[ { "id": "apoe-e3e4-farrer1997-caucasian", "gene": "APOE", "variant": "APOE e3/e4 genotype (rs429358 + rs7412 haplotypes)", "chromosome": "19", "position_hg38": 44908684, "risk_allele": "e4", "allele_frequency": 0.1379, "allele_frequency_source": "gnomAD genomes non-Finnish European via Ensembl release 116 (allele frequency of the defining SNP, not genotype frequency)", "effect_size": "OR 3.2 (95% CI 2.8-3.8) vs e3/e3", "effect_size_type": "odds ratio (genotype vs e3/e3)", "odds_ratio": 3.2, "ci_lower": 2.8, "ci_upper": 3.8, "p_value": null, "population": "Meta-analysis of 40 studies: 5,930 probable/definite AD cases and 8,607 non-demented controls (clinic, community and brain-bank sources); ORs adjusted for age and study", "ancestry": "European", "study_name": "Farrer et al. 1997, JAMA (APOE and Alzheimer Disease Meta Analysis Consortium)", "n_cases": 5930, "n_controls": 8607, "year": 1997, "url": "https://pubmed.ncbi.nlm.nih.gov/9343467/", "pubmed_id": "9343467", "classification": "high-risk", "category": "apoe", "value_type": "measured", "notes": "One copy of e4 (heterozygote) vs e3/e3, Caucasian clinic/autopsy-based series. APOE e4 is defined by rs429358-C together with rs7412-C. gnomAD genomes (Ensembl release 116) frequency of rs429358-C: African/African American 0.2157, non-Finnish European 0.1379, Admixed American 0.1133, South Asian 0.1046, East Asian 0.0977, Middle Eastern 0.0685. rs7412-T (e2-defining): African 0.1045, non-Finnish European 0.0794, East Asian 0.0801, Admixed American 0.0419." }, { "id": "apoe-e4e4-farrer1997-caucasian", "gene": "APOE", "variant": "APOE e4/e4 genotype (rs429358 + rs7412 haplotypes)", "chromosome": "19", "position_hg38": 44908684, "risk_allele": "e4", "allele_frequency": 0.1379, "allele_frequency_source": "gnomAD genomes non-Finnish European via Ensembl release 116 (allele frequency of the defining SNP, not genotype frequency)", "effect_size": "OR 14.9 (95% CI 10.8-20.6) vs e3/e3", "effect_size_type": "odds ratio (genotype vs e3/e3)", "odds_ratio": 14.9, "ci_lower": 10.8, "ci_upper": 20.6, "p_value": null, "population": "Meta-analysis of 40 studies: 5,930 probable/definite AD cases and 8,607 non-demented controls (clinic, community and brain-bank sources); ORs adjusted for age and study", "ancestry": "European", "study_name": "Farrer et al. 1997, JAMA (APOE and Alzheimer Disease Meta Analysis Consortium)", "n_cases": 5930, "n_controls": 8607, "year": 1997, "url": "https://pubmed.ncbi.nlm.nih.gov/9343467/", "pubmed_id": "9343467", "classification": "high-risk", "category": "apoe", "value_type": "measured", "notes": "Two copies of e4 (homozygote) vs e3/e3, Caucasian clinic/autopsy-based series. Compare e3/e4 OR 3.2: the dose effect is strongly super-additive. APOE e4 is defined by rs429358-C together with rs7412-C. gnomAD genomes (Ensembl release 116) frequency of rs429358-C: African/African American 0.2157, non-Finnish European 0.1379, Admixed American 0.1133, South Asian 0.1046, East Asian 0.0977, Middle Eastern 0.0685. rs7412-T (e2-defining): African 0.1045, non-Finnish European 0.0794, East Asian 0.0801, Admixed American 0.0419." }, { "id": "apoe-e2e4-farrer1997-caucasian", "gene": "APOE", "variant": "APOE e2/e4 genotype (rs429358 + rs7412 haplotypes)", "chromosome": "19", "position_hg38": 44908684, "risk_allele": "e4", "allele_frequency": 0.1379, "allele_frequency_source": "gnomAD genomes non-Finnish European via Ensembl release 116 (allele frequency of the defining SNP, not genotype frequency)", "effect_size": "OR 2.6 (95% CI 1.6-4.0) vs e3/e3", "effect_size_type": "odds ratio (genotype vs e3/e3)", "odds_ratio": 2.6, "ci_lower": 1.6, "ci_upper": 4.0, "p_value": null, "population": "Meta-analysis of 40 studies: 5,930 probable/definite AD cases and 8,607 non-demented controls (clinic, community and brain-bank sources); ORs adjusted for age and study", "ancestry": "European", "study_name": "Farrer et al. 1997, JAMA (APOE and Alzheimer Disease Meta Analysis Consortium)", "n_cases": 5930, "n_controls": 8607, "year": 1997, "url": "https://pubmed.ncbi.nlm.nih.gov/9343467/", "pubmed_id": "9343467", "classification": "moderate-risk", "category": "apoe", "value_type": "measured", "notes": "e2/e4 vs e3/e3, Caucasian. APOE e4 is defined by rs429358-C together with rs7412-C. gnomAD genomes (Ensembl release 116) frequency of rs429358-C: African/African American 0.2157, non-Finnish European 0.1379, Admixed American 0.1133, South Asian 0.1046, East Asian 0.0977, Middle Eastern 0.0685. rs7412-T (e2-defining): African 0.1045, non-Finnish European 0.0794, East Asian 0.0801, Admixed American 0.0419." }, { "id": "apoe-e2e3-farrer1997-caucasian", "gene": "APOE", "variant": "APOE e2/e3 genotype (rs429358 + rs7412 haplotypes)", "chromosome": "19", "position_hg38": 44908684, "risk_allele": "e2", "allele_frequency": 0.0794, "allele_frequency_source": "gnomAD genomes non-Finnish European via Ensembl release 116 (allele frequency of the defining SNP, not genotype frequency)", "effect_size": "OR 0.6 (95% CI 0.5-0.8) vs e3/e3", "effect_size_type": "odds ratio (genotype vs e3/e3)", "odds_ratio": 0.6, "ci_lower": 0.5, "ci_upper": 0.8, "p_value": null, "population": "Meta-analysis of 40 studies: 5,930 probable/definite AD cases and 8,607 non-demented controls (clinic, community and brain-bank sources); ORs adjusted for age and study", "ancestry": "European", "study_name": "Farrer et al. 1997, JAMA (APOE and Alzheimer Disease Meta Analysis Consortium)", "n_cases": 5930, "n_controls": 8607, "year": 1997, "url": "https://pubmed.ncbi.nlm.nih.gov/9343467/", "pubmed_id": "9343467", "classification": "protective", "category": "apoe", "value_type": "measured", "notes": "e2/e3 vs e3/e3, Caucasian. Abstract: 'The e2/e3 genotype appears equally protective across ethnic groups.' APOE e4 is defined by rs429358-C together with rs7412-C. gnomAD genomes (Ensembl release 116) frequency of rs429358-C: African/African American 0.2157, non-Finnish European 0.1379, Admixed American 0.1133, South Asian 0.1046, East Asian 0.0977, Middle Eastern 0.0685. rs7412-T (e2-defining): African 0.1045, non-Finnish European 0.0794, East Asian 0.0801, Admixed American 0.0419." }, { "id": "apoe-e2e2-farrer1997-caucasian", "gene": "APOE", "variant": "APOE e2/e2 genotype (rs429358 + rs7412 haplotypes)", "chromosome": "19", "position_hg38": 44908684, "risk_allele": "e2", "allele_frequency": 0.0794, "allele_frequency_source": "gnomAD genomes non-Finnish European via Ensembl release 116 (allele frequency of the defining SNP, not genotype frequency)", "effect_size": "OR 0.6 (95% CI 0.2-2.0) vs e3/e3", "effect_size_type": "odds ratio (genotype vs e3/e3)", "odds_ratio": 0.6, "ci_lower": 0.2, "ci_upper": 2.0, "p_value": null, "population": "Meta-analysis of 40 studies: 5,930 probable/definite AD cases and 8,607 non-demented controls (clinic, community and brain-bank sources); ORs adjusted for age and study", "ancestry": "European", "study_name": "Farrer et al. 1997, JAMA (APOE and Alzheimer Disease Meta Analysis Consortium)", "n_cases": 5930, "n_controls": 8607, "year": 1997, "url": "https://pubmed.ncbi.nlm.nih.gov/9343467/", "pubmed_id": "9343467", "classification": "protective", "category": "apoe", "value_type": "measured", "notes": "e2/e2 vs e3/e3, Caucasian; CI crosses 1 because e2 homozygotes are <1% of the population (see Reiman 2020 for a powered estimate). APOE e4 is defined by rs429358-C together with rs7412-C. gnomAD genomes (Ensembl release 116) frequency of rs429358-C: African/African American 0.2157, non-Finnish European 0.1379, Admixed American 0.1133, South Asian 0.1046, East Asian 0.0977, Middle Eastern 0.0685. rs7412-T (e2-defining): African 0.1045, non-Finnish European 0.0794, East Asian 0.0801, Admixed American 0.0419." }, { "id": "apoe-e3e4-farrer1997-japanese", "gene": "APOE", "variant": "APOE e3/e4 genotype", "chromosome": "19", "position_hg38": 44908684, "risk_allele": "e4", "allele_frequency": 0.0977, "allele_frequency_source": "gnomAD genomes East Asian via Ensembl release 116 (rs429358-C)", "effect_size": "OR 5.6 (95% CI 3.9-8.0) vs e3/e3", "effect_size_type": "odds ratio (genotype vs e3/e3)", "odds_ratio": 5.6, "ci_lower": 3.9, "ci_upper": 8.0, "p_value": null, "population": "Meta-analysis of 40 studies: 5,930 probable/definite AD cases and 8,607 non-demented controls (clinic, community and brain-bank sources); ORs adjusted for age and study", "ancestry": "East-Asian", "study_name": "Farrer et al. 1997, JAMA (APOE and Alzheimer Disease Meta Analysis Consortium)", "n_cases": 5930, "n_controls": 8607, "year": 1997, "url": "https://pubmed.ncbi.nlm.nih.gov/9343467/", "pubmed_id": "9343467", "classification": "high-risk", "category": "apoe", "value_type": "measured", "notes": "Japanese subjects; abstract: 'The APOE e4-AD association in Japanese subjects was stronger than in Caucasian subjects.' Abstract also states the association was weaker among African Americans and Hispanics with significant heterogeneity among African American studies (P<.03); the numeric AA/Hispanic ORs are in the paywalled full text and were NOT loaded, so they are not recorded here." }, { "id": "apoe-e4e4-farrer1997-japanese", "gene": "APOE", "variant": "APOE e4/e4 genotype", "chromosome": "19", "position_hg38": 44908684, "risk_allele": "e4", "allele_frequency": 0.0977, "allele_frequency_source": "gnomAD genomes East Asian via Ensembl release 116 (rs429358-C)", "effect_size": "OR 33.1 (95% CI 13.6-80.5) vs e3/e3", "effect_size_type": "odds ratio (genotype vs e3/e3)", "odds_ratio": 33.1, "ci_lower": 13.6, "ci_upper": 80.5, "p_value": null, "population": "Meta-analysis of 40 studies: 5,930 probable/definite AD cases and 8,607 non-demented controls (clinic, community and brain-bank sources); ORs adjusted for age and study", "ancestry": "East-Asian", "study_name": "Farrer et al. 1997, JAMA (APOE and Alzheimer Disease Meta Analysis Consortium)", "n_cases": 5930, "n_controls": 8607, "year": 1997, "url": "https://pubmed.ncbi.nlm.nih.gov/9343467/", "pubmed_id": "9343467", "classification": "high-risk", "category": "apoe", "value_type": "measured", "notes": "Japanese subjects; abstract: 'The APOE e4-AD association in Japanese subjects was stronger than in Caucasian subjects.' Abstract also states the association was weaker among African Americans and Hispanics with significant heterogeneity among African American studies (P<.03); the numeric AA/Hispanic ORs are in the paywalled full text and were NOT loaded, so they are not recorded here." }, { "id": "apoe-34-belloy2023-white", "gene": "APOE", "variant": "APOE*34 (rs429358/rs7412)", "chromosome": "19", "position_hg38": 44908684, "risk_allele": "e4", "allele_frequency": 0.1379, "allele_frequency_source": "gnomAD genomes nfe via Ensembl release 116 (rs429358-C allele frequency)", "effect_size": "OR 3.46 (95% CI 3.27-3.65) vs APOE*33", "effect_size_type": "odds ratio (genotype or allele dosage vs APOE*33)", "odds_ratio": 3.46, "ci_lower": 3.27, "ci_upper": 3.65, "p_value": null, "population": "non-Hispanic White individuals (n = 34,021; 59.3% female; mean age 77.0 y); case-control logistic regression, reference APOE*33", "ancestry": "European", "study_name": "Belloy et al. 2023, JAMA Neurol (ADSP/ADGC/A4/others; 68,756 individuals)", "n_cases": null, "n_controls": null, "year": 2023, "url": "https://doi.org/10.1001/jamaneurol.2023.3599", "pubmed_id": "37930705", "classification": "high-risk", "category": "apoe", "value_type": "measured", "notes": "Read from the paper's main Table (Europe PMC full text). Case/control split per group is not given in the abstract or table, so n_cases/n_controls are left empty; group n is in 'population'. Abstract: 'stepwise pattern' of APOE*34 ORs attenuating East Asian > White > Black > Hispanic; APOE*22+23 not associated with AD in East Asian or Hispanic individuals. Within Black individuals, more European global ancestry was associated with increasing APOE*4 risk. These ancestry differences are directly relevant to genetic-risk transferability and disparities work." }, { "id": "apoe-44-belloy2023-white", "gene": "APOE", "variant": "APOE*44 (rs429358/rs7412)", "chromosome": "19", "position_hg38": 44908684, "risk_allele": "e4", "allele_frequency": 0.1379, "allele_frequency_source": "gnomAD genomes nfe via Ensembl release 116 (rs429358-C allele frequency)", "effect_size": "OR 13.04 (95% CI 11.31-15.04) vs APOE*33", "effect_size_type": "odds ratio (genotype or allele dosage vs APOE*33)", "odds_ratio": 13.04, "ci_lower": 11.31, "ci_upper": 15.04, "p_value": null, "population": "non-Hispanic White individuals (n = 34,021; 59.3% female; mean age 77.0 y); case-control logistic regression, reference APOE*33", "ancestry": "European", "study_name": "Belloy et al. 2023, JAMA Neurol (ADSP/ADGC/A4/others; 68,756 individuals)", "n_cases": null, "n_controls": null, "year": 2023, "url": "https://doi.org/10.1001/jamaneurol.2023.3599", "pubmed_id": "37930705", "classification": "high-risk", "category": "apoe", "value_type": "measured", "notes": "Read from the paper's main Table (Europe PMC full text). Case/control split per group is not given in the abstract or table, so n_cases/n_controls are left empty; group n is in 'population'. Abstract: 'stepwise pattern' of APOE*34 ORs attenuating East Asian > White > Black > Hispanic; APOE*22+23 not associated with AD in East Asian or Hispanic individuals. Within Black individuals, more European global ancestry was associated with increasing APOE*4 risk. These ancestry differences are directly relevant to genetic-risk transferability and disparities work." }, { "id": "apoe-24-belloy2023-white", "gene": "APOE", "variant": "APOE*24 (rs429358/rs7412)", "chromosome": "19", "position_hg38": 44908684, "risk_allele": "e4", "allele_frequency": 0.1379, "allele_frequency_source": "gnomAD genomes nfe via Ensembl release 116 (rs429358-C allele frequency)", "effect_size": "OR 2.23 (95% CI 1.90-2.62) vs APOE*33", "effect_size_type": "odds ratio (genotype or allele dosage vs APOE*33)", "odds_ratio": 2.23, "ci_lower": 1.9, "ci_upper": 2.62, "p_value": null, "population": "non-Hispanic White individuals (n = 34,021; 59.3% female; mean age 77.0 y); case-control logistic regression, reference APOE*33", "ancestry": "European", "study_name": "Belloy et al. 2023, JAMA Neurol (ADSP/ADGC/A4/others; 68,756 individuals)", "n_cases": null, "n_controls": null, "year": 2023, "url": "https://doi.org/10.1001/jamaneurol.2023.3599", "pubmed_id": "37930705", "classification": "moderate-risk", "category": "apoe", "value_type": "measured", "notes": "Read from the paper's main Table (Europe PMC full text). Case/control split per group is not given in the abstract or table, so n_cases/n_controls are left empty; group n is in 'population'. Abstract: 'stepwise pattern' of APOE*34 ORs attenuating East Asian > White > Black > Hispanic; APOE*22+23 not associated with AD in East Asian or Hispanic individuals. Within Black individuals, more European global ancestry was associated with increasing APOE*4 risk. These ancestry differences are directly relevant to genetic-risk transferability and disparities work." }, { "id": "apoe-23-belloy2023-white", "gene": "APOE", "variant": "APOE*23 (rs429358/rs7412)", "chromosome": "19", "position_hg38": 44908684, "risk_allele": "e2", "allele_frequency": 0.0794, "allele_frequency_source": "gnomAD genomes nfe via Ensembl release 116 (rs7412-T allele frequency)", "effect_size": "OR 0.53 (95% CI 0.48-0.59) vs APOE*33", "effect_size_type": "odds ratio (genotype or allele dosage vs APOE*33)", "odds_ratio": 0.53, "ci_lower": 0.48, "ci_upper": 0.59, "p_value": null, "population": "non-Hispanic White individuals (n = 34,021; 59.3% female; mean age 77.0 y); case-control logistic regression, reference APOE*33", "ancestry": "European", "study_name": "Belloy et al. 2023, JAMA Neurol (ADSP/ADGC/A4/others; 68,756 individuals)", "n_cases": null, "n_controls": null, "year": 2023, "url": "https://doi.org/10.1001/jamaneurol.2023.3599", "pubmed_id": "37930705", "classification": "protective", "category": "apoe", "value_type": "measured", "notes": "Read from the paper's main Table (Europe PMC full text). Case/control split per group is not given in the abstract or table, so n_cases/n_controls are left empty; group n is in 'population'. Abstract: 'stepwise pattern' of APOE*34 ORs attenuating East Asian > White > Black > Hispanic; APOE*22+23 not associated with AD in East Asian or Hispanic individuals. Within Black individuals, more European global ancestry was associated with increasing APOE*4 risk. These ancestry differences are directly relevant to genetic-risk transferability and disparities work." }, { "id": "apoe-22-belloy2023-white", "gene": "APOE", "variant": "APOE*22 (rs429358/rs7412)", "chromosome": "19", "position_hg38": 44908684, "risk_allele": "e2", "allele_frequency": 0.0794, "allele_frequency_source": "gnomAD genomes nfe via Ensembl release 116 (rs7412-T allele frequency)", "effect_size": "OR 0.39 (95% CI 0.25-0.61) vs APOE*33", "effect_size_type": "odds ratio (genotype or allele dosage vs APOE*33)", "odds_ratio": 0.39, "ci_lower": 0.25, "ci_upper": 0.61, "p_value": null, "population": "non-Hispanic White individuals (n = 34,021; 59.3% female; mean age 77.0 y); case-control logistic regression, reference APOE*33", "ancestry": "European", "study_name": "Belloy et al. 2023, JAMA Neurol (ADSP/ADGC/A4/others; 68,756 individuals)", "n_cases": null, "n_controls": null, "year": 2023, "url": "https://doi.org/10.1001/jamaneurol.2023.3599", "pubmed_id": "37930705", "classification": "protective", "category": "apoe", "value_type": "measured", "notes": "Read from the paper's main Table (Europe PMC full text). Case/control split per group is not given in the abstract or table, so n_cases/n_controls are left empty; group n is in 'population'. Abstract: 'stepwise pattern' of APOE*34 ORs attenuating East Asian > White > Black > Hispanic; APOE*22+23 not associated with AD in East Asian or Hispanic individuals. Within Black individuals, more European global ancestry was associated with increasing APOE*4 risk. These ancestry differences are directly relevant to genetic-risk transferability and disparities work." }, { "id": "apoe-4dosage-belloy2023-white", "gene": "APOE", "variant": "APOE*4 dosage (rs429358/rs7412)", "chromosome": "19", "position_hg38": 44908684, "risk_allele": "e4", "allele_frequency": 0.1379, "allele_frequency_source": "gnomAD genomes nfe via Ensembl release 116 (rs429358-C allele frequency)", "effect_size": "OR 3.48 (95% CI 3.32-3.64) vs APOE*33", "effect_size_type": "odds ratio (genotype or allele dosage vs APOE*33)", "odds_ratio": 3.48, "ci_lower": 3.32, "ci_upper": 3.64, "p_value": null, "population": "non-Hispanic White individuals (n = 34,021; 59.3% female; mean age 77.0 y); case-control logistic regression, reference APOE*33", "ancestry": "European", "study_name": "Belloy et al. 2023, JAMA Neurol (ADSP/ADGC/A4/others; 68,756 individuals)", "n_cases": null, "n_controls": null, "year": 2023, "url": "https://doi.org/10.1001/jamaneurol.2023.3599", "pubmed_id": "37930705", "classification": "high-risk", "category": "apoe", "value_type": "measured", "notes": "Read from the paper's main Table (Europe PMC full text). Case/control split per group is not given in the abstract or table, so n_cases/n_controls are left empty; group n is in 'population'. Abstract: 'stepwise pattern' of APOE*34 ORs attenuating East Asian > White > Black > Hispanic; APOE*22+23 not associated with AD in East Asian or Hispanic individuals. Within Black individuals, more European global ancestry was associated with increasing APOE*4 risk. These ancestry differences are directly relevant to genetic-risk transferability and disparities work." }, { "id": "apoe-2dosage-belloy2023-white", "gene": "APOE", "variant": "APOE*2 dosage (rs429358/rs7412)", "chromosome": "19", "position_hg38": 44908684, "risk_allele": "e2", "allele_frequency": 0.0794, "allele_frequency_source": "gnomAD genomes nfe via Ensembl release 116 (rs7412-T allele frequency)", "effect_size": "OR 0.55 (95% CI 0.50-0.60) vs APOE*33", "effect_size_type": "odds ratio (genotype or allele dosage vs APOE*33)", "odds_ratio": 0.55, "ci_lower": 0.5, "ci_upper": 0.6, "p_value": null, "population": "non-Hispanic White individuals (n = 34,021; 59.3% female; mean age 77.0 y); case-control logistic regression, reference APOE*33", "ancestry": "European", "study_name": "Belloy et al. 2023, JAMA Neurol (ADSP/ADGC/A4/others; 68,756 individuals)", "n_cases": null, "n_controls": null, "year": 2023, "url": "https://doi.org/10.1001/jamaneurol.2023.3599", "pubmed_id": "37930705", "classification": "protective", "category": "apoe", "value_type": "measured", "notes": "Read from the paper's main Table (Europe PMC full text). Case/control split per group is not given in the abstract or table, so n_cases/n_controls are left empty; group n is in 'population'. Abstract: 'stepwise pattern' of APOE*34 ORs attenuating East Asian > White > Black > Hispanic; APOE*22+23 not associated with AD in East Asian or Hispanic individuals. Within Black individuals, more European global ancestry was associated with increasing APOE*4 risk. These ancestry differences are directly relevant to genetic-risk transferability and disparities work." }, { "id": "apoe-34-belloy2023-black", "gene": "APOE", "variant": "APOE*34 (rs429358/rs7412)", "chromosome": "19", "position_hg38": 44908684, "risk_allele": "e4", "allele_frequency": 0.2157, "allele_frequency_source": "gnomAD genomes afr via Ensembl release 116 (rs429358-C allele frequency)", "effect_size": "OR 2.18 (95% CI 1.90-2.49) vs APOE*33", "effect_size_type": "odds ratio (genotype or allele dosage vs APOE*33)", "odds_ratio": 2.18, "ci_lower": 1.9, "ci_upper": 2.49, "p_value": null, "population": "non-Hispanic Black individuals (n = 7,145; 70.8% female; mean age 78.4 y); reference APOE*33", "ancestry": "African", "study_name": "Belloy et al. 2023, JAMA Neurol (ADSP/ADGC/A4/others; 68,756 individuals)", "n_cases": null, "n_controls": null, "year": 2023, "url": "https://doi.org/10.1001/jamaneurol.2023.3599", "pubmed_id": "37930705", "classification": "high-risk", "category": "apoe", "value_type": "measured", "notes": "Read from the paper's main Table (Europe PMC full text). Case/control split per group is not given in the abstract or table, so n_cases/n_controls are left empty; group n is in 'population'. Abstract: 'stepwise pattern' of APOE*34 ORs attenuating East Asian > White > Black > Hispanic; APOE*22+23 not associated with AD in East Asian or Hispanic individuals. Within Black individuals, more European global ancestry was associated with increasing APOE*4 risk. These ancestry differences are directly relevant to genetic-risk transferability and disparities work." }, { "id": "apoe-44-belloy2023-black", "gene": "APOE", "variant": "APOE*44 (rs429358/rs7412)", "chromosome": "19", "position_hg38": 44908684, "risk_allele": "e4", "allele_frequency": 0.2157, "allele_frequency_source": "gnomAD genomes afr via Ensembl release 116 (rs429358-C allele frequency)", "effect_size": "OR 6.49 (95% CI 5.07-8.31) vs APOE*33", "effect_size_type": "odds ratio (genotype or allele dosage vs APOE*33)", "odds_ratio": 6.49, "ci_lower": 5.07, "ci_upper": 8.31, "p_value": null, "population": "non-Hispanic Black individuals (n = 7,145; 70.8% female; mean age 78.4 y); reference APOE*33", "ancestry": "African", "study_name": "Belloy et al. 2023, JAMA Neurol (ADSP/ADGC/A4/others; 68,756 individuals)", "n_cases": null, "n_controls": null, "year": 2023, "url": "https://doi.org/10.1001/jamaneurol.2023.3599", "pubmed_id": "37930705", "classification": "high-risk", "category": "apoe", "value_type": "measured", "notes": "Read from the paper's main Table (Europe PMC full text). Case/control split per group is not given in the abstract or table, so n_cases/n_controls are left empty; group n is in 'population'. Abstract: 'stepwise pattern' of APOE*34 ORs attenuating East Asian > White > Black > Hispanic; APOE*22+23 not associated with AD in East Asian or Hispanic individuals. Within Black individuals, more European global ancestry was associated with increasing APOE*4 risk. These ancestry differences are directly relevant to genetic-risk transferability and disparities work." }, { "id": "apoe-24-belloy2023-black", "gene": "APOE", "variant": "APOE*24 (rs429358/rs7412)", "chromosome": "19", "position_hg38": 44908684, "risk_allele": "e4", "allele_frequency": 0.2157, "allele_frequency_source": "gnomAD genomes afr via Ensembl release 116 (rs429358-C allele frequency)", "effect_size": "OR 1.63 (95% CI 1.24-2.13) vs APOE*33", "effect_size_type": "odds ratio (genotype or allele dosage vs APOE*33)", "odds_ratio": 1.63, "ci_lower": 1.24, "ci_upper": 2.13, "p_value": null, "population": "non-Hispanic Black individuals (n = 7,145; 70.8% female; mean age 78.4 y); reference APOE*33", "ancestry": "African", "study_name": "Belloy et al. 2023, JAMA Neurol (ADSP/ADGC/A4/others; 68,756 individuals)", "n_cases": null, "n_controls": null, "year": 2023, "url": "https://doi.org/10.1001/jamaneurol.2023.3599", "pubmed_id": "37930705", "classification": "moderate-risk", "category": "apoe", "value_type": "measured", "notes": "Read from the paper's main Table (Europe PMC full text). Case/control split per group is not given in the abstract or table, so n_cases/n_controls are left empty; group n is in 'population'. Abstract: 'stepwise pattern' of APOE*34 ORs attenuating East Asian > White > Black > Hispanic; APOE*22+23 not associated with AD in East Asian or Hispanic individuals. Within Black individuals, more European global ancestry was associated with increasing APOE*4 risk. These ancestry differences are directly relevant to genetic-risk transferability and disparities work." }, { "id": "apoe-23-belloy2023-black", "gene": "APOE", "variant": "APOE*23 (rs429358/rs7412)", "chromosome": "19", "position_hg38": 44908684, "risk_allele": "e2", "allele_frequency": 0.1045, "allele_frequency_source": "gnomAD genomes afr via Ensembl release 116 (rs7412-T allele frequency)", "effect_size": "OR 0.69 (95% CI 0.56-0.84) vs APOE*33", "effect_size_type": "odds ratio (genotype or allele dosage vs APOE*33)", "odds_ratio": 0.69, "ci_lower": 0.56, "ci_upper": 0.84, "p_value": null, "population": "non-Hispanic Black individuals (n = 7,145; 70.8% female; mean age 78.4 y); reference APOE*33", "ancestry": "African", "study_name": "Belloy et al. 2023, JAMA Neurol (ADSP/ADGC/A4/others; 68,756 individuals)", "n_cases": null, "n_controls": null, "year": 2023, "url": "https://doi.org/10.1001/jamaneurol.2023.3599", "pubmed_id": "37930705", "classification": "protective", "category": "apoe", "value_type": "measured", "notes": "Read from the paper's main Table (Europe PMC full text). Case/control split per group is not given in the abstract or table, so n_cases/n_controls are left empty; group n is in 'population'. Abstract: 'stepwise pattern' of APOE*34 ORs attenuating East Asian > White > Black > Hispanic; APOE*22+23 not associated with AD in East Asian or Hispanic individuals. Within Black individuals, more European global ancestry was associated with increasing APOE*4 risk. These ancestry differences are directly relevant to genetic-risk transferability and disparities work." }, { "id": "apoe-22-belloy2023-black", "gene": "APOE", "variant": "APOE*22 (rs429358/rs7412)", "chromosome": "19", "position_hg38": 44908684, "risk_allele": "e2", "allele_frequency": 0.1045, "allele_frequency_source": "gnomAD genomes afr via Ensembl release 116 (rs7412-T allele frequency)", "effect_size": "OR 0.78 (95% CI 0.38-1.58) vs APOE*33", "effect_size_type": "odds ratio (genotype or allele dosage vs APOE*33)", "odds_ratio": 0.78, "ci_lower": 0.38, "ci_upper": 1.58, "p_value": null, "population": "non-Hispanic Black individuals (n = 7,145; 70.8% female; mean age 78.4 y); reference APOE*33", "ancestry": "African", "study_name": "Belloy et al. 2023, JAMA Neurol (ADSP/ADGC/A4/others; 68,756 individuals)", "n_cases": null, "n_controls": null, "year": 2023, "url": "https://doi.org/10.1001/jamaneurol.2023.3599", "pubmed_id": "37930705", "classification": "protective", "category": "apoe", "value_type": "measured", "notes": "Read from the paper's main Table (Europe PMC full text). Case/control split per group is not given in the abstract or table, so n_cases/n_controls are left empty; group n is in 'population'. Abstract: 'stepwise pattern' of APOE*34 ORs attenuating East Asian > White > Black > Hispanic; APOE*22+23 not associated with AD in East Asian or Hispanic individuals. Within Black individuals, more European global ancestry was associated with increasing APOE*4 risk. These ancestry differences are directly relevant to genetic-risk transferability and disparities work." }, { "id": "apoe-4dosage-belloy2023-black", "gene": "APOE", "variant": "APOE*4 dosage (rs429358/rs7412)", "chromosome": "19", "position_hg38": 44908684, "risk_allele": "e4", "allele_frequency": 0.2157, "allele_frequency_source": "gnomAD genomes afr via Ensembl release 116 (rs429358-C allele frequency)", "effect_size": "OR 2.39 (95% CI 2.16-2.65) vs APOE*33", "effect_size_type": "odds ratio (genotype or allele dosage vs APOE*33)", "odds_ratio": 2.39, "ci_lower": 2.16, "ci_upper": 2.65, "p_value": null, "population": "non-Hispanic Black individuals (n = 7,145; 70.8% female; mean age 78.4 y); reference APOE*33", "ancestry": "African", "study_name": "Belloy et al. 2023, JAMA Neurol (ADSP/ADGC/A4/others; 68,756 individuals)", "n_cases": null, "n_controls": null, "year": 2023, "url": "https://doi.org/10.1001/jamaneurol.2023.3599", "pubmed_id": "37930705", "classification": "high-risk", "category": "apoe", "value_type": "measured", "notes": "Read from the paper's main Table (Europe PMC full text). Case/control split per group is not given in the abstract or table, so n_cases/n_controls are left empty; group n is in 'population'. Abstract: 'stepwise pattern' of APOE*34 ORs attenuating East Asian > White > Black > Hispanic; APOE*22+23 not associated with AD in East Asian or Hispanic individuals. Within Black individuals, more European global ancestry was associated with increasing APOE*4 risk. These ancestry differences are directly relevant to genetic-risk transferability and disparities work." }, { "id": "apoe-2dosage-belloy2023-black", "gene": "APOE", "variant": "APOE*2 dosage (rs429358/rs7412)", "chromosome": "19", "position_hg38": 44908684, "risk_allele": "e2", "allele_frequency": 0.1045, "allele_frequency_source": "gnomAD genomes afr via Ensembl release 116 (rs7412-T allele frequency)", "effect_size": "OR 0.72 (95% CI 0.60-0.86) vs APOE*33", "effect_size_type": "odds ratio (genotype or allele dosage vs APOE*33)", "odds_ratio": 0.72, "ci_lower": 0.6, "ci_upper": 0.86, "p_value": null, "population": "non-Hispanic Black individuals (n = 7,145; 70.8% female; mean age 78.4 y); reference APOE*33", "ancestry": "African", "study_name": "Belloy et al. 2023, JAMA Neurol (ADSP/ADGC/A4/others; 68,756 individuals)", "n_cases": null, "n_controls": null, "year": 2023, "url": "https://doi.org/10.1001/jamaneurol.2023.3599", "pubmed_id": "37930705", "classification": "protective", "category": "apoe", "value_type": "measured", "notes": "Read from the paper's main Table (Europe PMC full text). Case/control split per group is not given in the abstract or table, so n_cases/n_controls are left empty; group n is in 'population'. Abstract: 'stepwise pattern' of APOE*34 ORs attenuating East Asian > White > Black > Hispanic; APOE*22+23 not associated with AD in East Asian or Hispanic individuals. Within Black individuals, more European global ancestry was associated with increasing APOE*4 risk. These ancestry differences are directly relevant to genetic-risk transferability and disparities work." }, { "id": "apoe-34-belloy2023-hispanic", "gene": "APOE", "variant": "APOE*34 (rs429358/rs7412)", "chromosome": "19", "position_hg38": 44908684, "risk_allele": "e4", "allele_frequency": 0.1133, "allele_frequency_source": "gnomAD genomes amr via Ensembl release 116 (rs429358-C allele frequency)", "effect_size": "OR 1.90 (95% CI 1.65-2.18) vs APOE*33", "effect_size_type": "odds ratio (genotype or allele dosage vs APOE*33)", "odds_ratio": 1.9, "ci_lower": 1.65, "ci_upper": 2.18, "p_value": null, "population": "Hispanic individuals, all races (n = 5,738; 68.2% female; mean age 75.4 y); reference APOE*33", "ancestry": "Hispanic", "study_name": "Belloy et al. 2023, JAMA Neurol (ADSP/ADGC/A4/others; 68,756 individuals)", "n_cases": null, "n_controls": null, "year": 2023, "url": "https://doi.org/10.1001/jamaneurol.2023.3599", "pubmed_id": "37930705", "classification": "moderate-risk", "category": "apoe", "value_type": "measured", "notes": "Read from the paper's main Table (Europe PMC full text). Case/control split per group is not given in the abstract or table, so n_cases/n_controls are left empty; group n is in 'population'. Abstract: 'stepwise pattern' of APOE*34 ORs attenuating East Asian > White > Black > Hispanic; APOE*22+23 not associated with AD in East Asian or Hispanic individuals. Within Black individuals, more European global ancestry was associated with increasing APOE*4 risk. These ancestry differences are directly relevant to genetic-risk transferability and disparities work." }, { "id": "apoe-44-belloy2023-hispanic", "gene": "APOE", "variant": "APOE*44 (rs429358/rs7412)", "chromosome": "19", "position_hg38": 44908684, "risk_allele": "e4", "allele_frequency": 0.1133, "allele_frequency_source": "gnomAD genomes amr via Ensembl release 116 (rs429358-C allele frequency)", "effect_size": "OR 3.62 (95% CI 2.56-5.11) vs APOE*33", "effect_size_type": "odds ratio (genotype or allele dosage vs APOE*33)", "odds_ratio": 3.62, "ci_lower": 2.56, "ci_upper": 5.11, "p_value": null, "population": "Hispanic individuals, all races (n = 5,738; 68.2% female; mean age 75.4 y); reference APOE*33", "ancestry": "Hispanic", "study_name": "Belloy et al. 2023, JAMA Neurol (ADSP/ADGC/A4/others; 68,756 individuals)", "n_cases": null, "n_controls": null, "year": 2023, "url": "https://doi.org/10.1001/jamaneurol.2023.3599", "pubmed_id": "37930705", "classification": "high-risk", "category": "apoe", "value_type": "measured", "notes": "Read from the paper's main Table (Europe PMC full text). Case/control split per group is not given in the abstract or table, so n_cases/n_controls are left empty; group n is in 'population'. Abstract: 'stepwise pattern' of APOE*34 ORs attenuating East Asian > White > Black > Hispanic; APOE*22+23 not associated with AD in East Asian or Hispanic individuals. Within Black individuals, more European global ancestry was associated with increasing APOE*4 risk. These ancestry differences are directly relevant to genetic-risk transferability and disparities work." }, { "id": "apoe-24-belloy2023-hispanic", "gene": "APOE", "variant": "APOE*24 (rs429358/rs7412)", "chromosome": "19", "position_hg38": 44908684, "risk_allele": "e4", "allele_frequency": 0.1133, "allele_frequency_source": "gnomAD genomes amr via Ensembl release 116 (rs429358-C allele frequency)", "effect_size": "OR 1.11 (95% CI 0.72-1.72) vs APOE*33", "effect_size_type": "odds ratio (genotype or allele dosage vs APOE*33)", "odds_ratio": 1.11, "ci_lower": 0.72, "ci_upper": 1.72, "p_value": null, "population": "Hispanic individuals, all races (n = 5,738; 68.2% female; mean age 75.4 y); reference APOE*33", "ancestry": "Hispanic", "study_name": "Belloy et al. 2023, JAMA Neurol (ADSP/ADGC/A4/others; 68,756 individuals)", "n_cases": null, "n_controls": null, "year": 2023, "url": "https://doi.org/10.1001/jamaneurol.2023.3599", "pubmed_id": "37930705", "classification": "disputed", "category": "apoe", "value_type": "measured", "notes": "Read from the paper's main Table (Europe PMC full text). Case/control split per group is not given in the abstract or table, so n_cases/n_controls are left empty; group n is in 'population'. Abstract: 'stepwise pattern' of APOE*34 ORs attenuating East Asian > White > Black > Hispanic; APOE*22+23 not associated with AD in East Asian or Hispanic individuals. Within Black individuals, more European global ancestry was associated with increasing APOE*4 risk. These ancestry differences are directly relevant to genetic-risk transferability and disparities work." }, { "id": "apoe-23-belloy2023-hispanic", "gene": "APOE", "variant": "APOE*23 (rs429358/rs7412)", "chromosome": "19", "position_hg38": 44908684, "risk_allele": "e2", "allele_frequency": 0.0419, "allele_frequency_source": "gnomAD genomes amr via Ensembl release 116 (rs7412-T allele frequency)", "effect_size": "OR 0.89 (95% CI 0.71-1.10) vs APOE*33", "effect_size_type": "odds ratio (genotype or allele dosage vs APOE*33)", "odds_ratio": 0.89, "ci_lower": 0.71, "ci_upper": 1.1, "p_value": null, "population": "Hispanic individuals, all races (n = 5,738; 68.2% female; mean age 75.4 y); reference APOE*33", "ancestry": "Hispanic", "study_name": "Belloy et al. 2023, JAMA Neurol (ADSP/ADGC/A4/others; 68,756 individuals)", "n_cases": null, "n_controls": null, "year": 2023, "url": "https://doi.org/10.1001/jamaneurol.2023.3599", "pubmed_id": "37930705", "classification": "disputed", "category": "apoe", "value_type": "measured", "notes": "Read from the paper's main Table (Europe PMC full text). Case/control split per group is not given in the abstract or table, so n_cases/n_controls are left empty; group n is in 'population'. Abstract: 'stepwise pattern' of APOE*34 ORs attenuating East Asian > White > Black > Hispanic; APOE*22+23 not associated with AD in East Asian or Hispanic individuals. Within Black individuals, more European global ancestry was associated with increasing APOE*4 risk. These ancestry differences are directly relevant to genetic-risk transferability and disparities work." }, { "id": "apoe-22-belloy2023-hispanic", "gene": "APOE", "variant": "APOE*22 (rs429358/rs7412)", "chromosome": "19", "position_hg38": 44908684, "risk_allele": "e2", "allele_frequency": 0.0419, "allele_frequency_source": "gnomAD genomes amr via Ensembl release 116 (rs7412-T allele frequency)", "effect_size": "OR 1.02 (95% CI 0.41-2.51) vs APOE*33", "effect_size_type": "odds ratio (genotype or allele dosage vs APOE*33)", "odds_ratio": 1.02, "ci_lower": 0.41, "ci_upper": 2.51, "p_value": null, "population": "Hispanic individuals, all races (n = 5,738; 68.2% female; mean age 75.4 y); reference APOE*33", "ancestry": "Hispanic", "study_name": "Belloy et al. 2023, JAMA Neurol (ADSP/ADGC/A4/others; 68,756 individuals)", "n_cases": null, "n_controls": null, "year": 2023, "url": "https://doi.org/10.1001/jamaneurol.2023.3599", "pubmed_id": "37930705", "classification": "disputed", "category": "apoe", "value_type": "measured", "notes": "Read from the paper's main Table (Europe PMC full text). Case/control split per group is not given in the abstract or table, so n_cases/n_controls are left empty; group n is in 'population'. Abstract: 'stepwise pattern' of APOE*34 ORs attenuating East Asian > White > Black > Hispanic; APOE*22+23 not associated with AD in East Asian or Hispanic individuals. Within Black individuals, more European global ancestry was associated with increasing APOE*4 risk. These ancestry differences are directly relevant to genetic-risk transferability and disparities work." }, { "id": "apoe-4dosage-belloy2023-hispanic", "gene": "APOE", "variant": "APOE*4 dosage (rs429358/rs7412)", "chromosome": "19", "position_hg38": 44908684, "risk_allele": "e4", "allele_frequency": 0.1133, "allele_frequency_source": "gnomAD genomes amr via Ensembl release 116 (rs429358-C allele frequency)", "effect_size": "OR 1.90 (95% CI 1.70-2.13) vs APOE*33", "effect_size_type": "odds ratio (genotype or allele dosage vs APOE*33)", "odds_ratio": 1.9, "ci_lower": 1.7, "ci_upper": 2.13, "p_value": null, "population": "Hispanic individuals, all races (n = 5,738; 68.2% female; mean age 75.4 y); reference APOE*33", "ancestry": "Hispanic", "study_name": "Belloy et al. 2023, JAMA Neurol (ADSP/ADGC/A4/others; 68,756 individuals)", "n_cases": null, "n_controls": null, "year": 2023, "url": "https://doi.org/10.1001/jamaneurol.2023.3599", "pubmed_id": "37930705", "classification": "moderate-risk", "category": "apoe", "value_type": "measured", "notes": "Read from the paper's main Table (Europe PMC full text). Case/control split per group is not given in the abstract or table, so n_cases/n_controls are left empty; group n is in 'population'. Abstract: 'stepwise pattern' of APOE*34 ORs attenuating East Asian > White > Black > Hispanic; APOE*22+23 not associated with AD in East Asian or Hispanic individuals. Within Black individuals, more European global ancestry was associated with increasing APOE*4 risk. These ancestry differences are directly relevant to genetic-risk transferability and disparities work." }, { "id": "apoe-2dosage-belloy2023-hispanic", "gene": "APOE", "variant": "APOE*2 dosage (rs429358/rs7412)", "chromosome": "19", "position_hg38": 44908684, "risk_allele": "e2", "allele_frequency": 0.0419, "allele_frequency_source": "gnomAD genomes amr via Ensembl release 116 (rs7412-T allele frequency)", "effect_size": "OR 0.90 (95% CI 0.74-1.10) vs APOE*33", "effect_size_type": "odds ratio (genotype or allele dosage vs APOE*33)", "odds_ratio": 0.9, "ci_lower": 0.74, "ci_upper": 1.1, "p_value": null, "population": "Hispanic individuals, all races (n = 5,738; 68.2% female; mean age 75.4 y); reference APOE*33", "ancestry": "Hispanic", "study_name": "Belloy et al. 2023, JAMA Neurol (ADSP/ADGC/A4/others; 68,756 individuals)", "n_cases": null, "n_controls": null, "year": 2023, "url": "https://doi.org/10.1001/jamaneurol.2023.3599", "pubmed_id": "37930705", "classification": "disputed", "category": "apoe", "value_type": "measured", "notes": "Read from the paper's main Table (Europe PMC full text). Case/control split per group is not given in the abstract or table, so n_cases/n_controls are left empty; group n is in 'population'. Abstract: 'stepwise pattern' of APOE*34 ORs attenuating East Asian > White > Black > Hispanic; APOE*22+23 not associated with AD in East Asian or Hispanic individuals. Within Black individuals, more European global ancestry was associated with increasing APOE*4 risk. These ancestry differences are directly relevant to genetic-risk transferability and disparities work." }, { "id": "apoe-34-belloy2023-eastasian", "gene": "APOE", "variant": "APOE*34 (rs429358/rs7412)", "chromosome": "19", "position_hg38": 44908684, "risk_allele": "e4", "allele_frequency": 0.0977, "allele_frequency_source": "gnomAD genomes eas via Ensembl release 116 (rs429358-C allele frequency)", "effect_size": "OR 4.54 (95% CI 3.99-5.17) vs APOE*33", "effect_size_type": "odds ratio (genotype or allele dosage vs APOE*33)", "odds_ratio": 4.54, "ci_lower": 3.99, "ci_upper": 5.17, "p_value": null, "population": "East Asian individuals (n = 21,852; summary statistics from published studies; demographic data not available); reference APOE*33", "ancestry": "East-Asian", "study_name": "Belloy et al. 2023, JAMA Neurol (ADSP/ADGC/A4/others; 68,756 individuals)", "n_cases": null, "n_controls": null, "year": 2023, "url": "https://doi.org/10.1001/jamaneurol.2023.3599", "pubmed_id": "37930705", "classification": "high-risk", "category": "apoe", "value_type": "measured", "notes": "Read from the paper's main Table (Europe PMC full text). Case/control split per group is not given in the abstract or table, so n_cases/n_controls are left empty; group n is in 'population'. Abstract: 'stepwise pattern' of APOE*34 ORs attenuating East Asian > White > Black > Hispanic; APOE*22+23 not associated with AD in East Asian or Hispanic individuals. Within Black individuals, more European global ancestry was associated with increasing APOE*4 risk. These ancestry differences are directly relevant to genetic-risk transferability and disparities work." }, { "id": "apoe-2223-belloy2023-eastasian", "gene": "APOE", "variant": "APOE*22+23 (rs429358/rs7412)", "chromosome": "19", "position_hg38": 44908684, "risk_allele": "e2", "allele_frequency": 0.0801, "allele_frequency_source": "gnomAD genomes eas via Ensembl release 116 (rs7412-T allele frequency)", "effect_size": "OR 0.97 (95% CI 0.77-1.23) vs APOE*33", "effect_size_type": "odds ratio (genotype or allele dosage vs APOE*33)", "odds_ratio": 0.97, "ci_lower": 0.77, "ci_upper": 1.23, "p_value": null, "population": "East Asian individuals (n = 21,852; summary statistics from published studies; demographic data not available); reference APOE*33", "ancestry": "East-Asian", "study_name": "Belloy et al. 2023, JAMA Neurol (ADSP/ADGC/A4/others; 68,756 individuals)", "n_cases": null, "n_controls": null, "year": 2023, "url": "https://doi.org/10.1001/jamaneurol.2023.3599", "pubmed_id": "37930705", "classification": "disputed", "category": "apoe", "value_type": "measured", "notes": "Read from the paper's main Table (Europe PMC full text). Case/control split per group is not given in the abstract or table, so n_cases/n_controls are left empty; group n is in 'population'. Abstract: 'stepwise pattern' of APOE*34 ORs attenuating East Asian > White > Black > Hispanic; APOE*22+23 not associated with AD in East Asian or Hispanic individuals. Within Black individuals, more European global ancestry was associated with increasing APOE*4 risk. These ancestry differences are directly relevant to genetic-risk transferability and disparities work." }, { "id": "apoe-e2e2-vs-e3e3-reiman2020", "gene": "APOE", "variant": "APOE e2/e2 vs e3/e3", "chromosome": "19", "position_hg38": 44908684, "risk_allele": "e2", "allele_frequency": 0.0794, "allele_frequency_source": "gnomAD genomes non-Finnish European via Ensembl release 116", "effect_size": "OR 0.13 (95% CI 0.05-0.36)", "effect_size_type": "odds ratio (genotype comparison as stated)", "odds_ratio": 0.13, "ci_lower": 0.05, "ci_upper": 0.36, "p_value": null, "population": "More than 5,000 clinically and neuropathologically characterized AD dementia cases and controls (ADGC); ORs from logistic regression; predominantly European-ancestry ADGC autopsy series (ancestry composition not stated in abstract)", "ancestry": "European", "study_name": "Reiman et al. 2020, Nat Commun (ADGC neuropathologically confirmed cases and controls)", "n_cases": null, "n_controls": null, "year": 2020, "url": "https://doi.org/10.1038/s41467-019-14279-8", "pubmed_id": "32015339", "classification": "protective", "category": "apoe", "value_type": "measured", "notes": "Text: 'APOE2 homozygotes ... had ... an extremely low 0.13 OR (95% CI 0.05-0.36) compared to the most common APOE3/3 genotype'. In the clinical (unconfirmed) group the e2/e2 vs e3/e3 OR was 0.52 (0.30-0.90)." }, { "id": "apoe-e2e2-vs-e2e3-reiman2020", "gene": "APOE", "variant": "APOE e2/e2 vs e2/e3", "chromosome": "19", "position_hg38": 44908684, "risk_allele": "e2", "allele_frequency": 0.0794, "allele_frequency_source": "gnomAD genomes non-Finnish European via Ensembl release 116", "effect_size": "OR 0.34 (95% CI 0.12-0.95)", "effect_size_type": "odds ratio (genotype comparison as stated)", "odds_ratio": 0.34, "ci_lower": 0.12, "ci_upper": 0.95, "p_value": null, "population": "More than 5,000 clinically and neuropathologically characterized AD dementia cases and controls (ADGC); ORs from logistic regression; predominantly European-ancestry ADGC autopsy series (ancestry composition not stated in abstract)", "ancestry": "European", "study_name": "Reiman et al. 2020, Nat Commun (ADGC neuropathologically confirmed cases and controls)", "n_cases": null, "n_controls": null, "year": 2020, "url": "https://doi.org/10.1038/s41467-019-14279-8", "pubmed_id": "32015339", "classification": "protective", "category": "apoe", "value_type": "measured", "notes": "Table 2: e2 homozygotes have lower odds than e2/e3 heterozygotes, i.e. a dose effect for e2 as well." }, { "id": "apoe-e2e2-vs-e4e4-reiman2020", "gene": "APOE", "variant": "APOE e2/e2 vs e4/e4", "chromosome": "19", "position_hg38": 44908684, "risk_allele": "e2", "allele_frequency": 0.0794, "allele_frequency_source": "gnomAD genomes non-Finnish European via Ensembl release 116", "effect_size": "OR 0.004 (95% CI 0.001-0.014)", "effect_size_type": "odds ratio (genotype comparison as stated)", "odds_ratio": 0.004, "ci_lower": 0.001, "ci_upper": 0.014, "p_value": null, "population": "More than 5,000 clinically and neuropathologically characterized AD dementia cases and controls (ADGC); ORs from logistic regression; predominantly European-ancestry ADGC autopsy series (ancestry composition not stated in abstract)", "ancestry": "European", "study_name": "Reiman et al. 2020, Nat Commun (ADGC neuropathologically confirmed cases and controls)", "n_cases": null, "n_controls": null, "year": 2020, "url": "https://doi.org/10.1038/s41467-019-14279-8", "pubmed_id": "32015339", "classification": "protective", "category": "apoe", "value_type": "measured", "notes": "Table 2: the full span of APOE genotype risk in autopsy-confirmed material." }, { "id": "apoe-e3e4-vs-e2e3-reiman2020", "gene": "APOE", "variant": "APOE e3/e4 vs e2/e3", "chromosome": "19", "position_hg38": 44908684, "risk_allele": "e4", "allele_frequency": 0.1379, "allele_frequency_source": "gnomAD genomes non-Finnish European via Ensembl release 116", "effect_size": "OR 15.92 (95% CI 11.85-21.38)", "effect_size_type": "odds ratio (genotype comparison as stated)", "odds_ratio": 15.92, "ci_lower": 11.85, "ci_upper": 21.38, "p_value": null, "population": "More than 5,000 clinically and neuropathologically characterized AD dementia cases and controls (ADGC); ORs from logistic regression; predominantly European-ancestry ADGC autopsy series (ancestry composition not stated in abstract)", "ancestry": "European", "study_name": "Reiman et al. 2020, Nat Commun (ADGC neuropathologically confirmed cases and controls)", "n_cases": null, "n_controls": null, "year": 2020, "url": "https://doi.org/10.1038/s41467-019-14279-8", "pubmed_id": "32015339", "classification": "high-risk", "category": "apoe", "value_type": "measured", "notes": "Table 2 uses e2/e3 as reference; e3/e3 vs e2/e3 = 2.60 (2.00-3.38), e2/e4 = 6.96 (4.06-11.92)." }, { "id": "apoe-e4e4-vs-e2e3-reiman2020", "gene": "APOE", "variant": "APOE e4/e4 vs e2/e3", "chromosome": "19", "position_hg38": 44908684, "risk_allele": "e4", "allele_frequency": 0.1379, "allele_frequency_source": "gnomAD genomes non-Finnish European via Ensembl release 116", "effect_size": "OR 81.05 (95% CI 41.39-158.68)", "effect_size_type": "odds ratio (genotype comparison as stated)", "odds_ratio": 81.05, "ci_lower": 41.39, "ci_upper": 158.68, "p_value": null, "population": "More than 5,000 clinically and neuropathologically characterized AD dementia cases and controls (ADGC); ORs from logistic regression; predominantly European-ancestry ADGC autopsy series (ancestry composition not stated in abstract)", "ancestry": "European", "study_name": "Reiman et al. 2020, Nat Commun (ADGC neuropathologically confirmed cases and controls)", "n_cases": null, "n_controls": null, "year": 2020, "url": "https://doi.org/10.1038/s41467-019-14279-8", "pubmed_id": "32015339", "classification": "high-risk", "category": "apoe", "value_type": "measured", "notes": "Table 2. Mean onset age in neuropath-confirmed cases: 69.9 +/- 6.1 y (e4/e4) to 79.3 +/- 9.0 y (e2/e3 + e2/e2)." }, { "id": "apoe-e4-allelic-dose-reiman2020", "gene": "APOE", "variant": "APOE e4 allele dose (additive model, e2 non-carriers)", "chromosome": "19", "position_hg38": 44908684, "risk_allele": "e4", "allele_frequency": 0.1379, "allele_frequency_source": "gnomAD genomes non-Finnish European via Ensembl release 116", "effect_size": "OR 6.00 per e4 allele (neuropathologically confirmed group)", "effect_size_type": "odds ratio (genotype comparison as stated)", "odds_ratio": 6.0, "ci_lower": null, "ci_upper": null, "p_value": null, "population": "More than 5,000 clinically and neuropathologically characterized AD dementia cases and controls (ADGC); ORs from logistic regression; predominantly European-ancestry ADGC autopsy series (ancestry composition not stated in abstract)", "ancestry": "European", "study_name": "Reiman et al. 2020, Nat Commun (ADGC neuropathologically confirmed cases and controls)", "n_cases": null, "n_controls": null, "year": 2020, "url": "https://doi.org/10.1038/s41467-019-14279-8", "pubmed_id": "32015339", "classification": "high-risk", "category": "apoe", "value_type": "measured", "notes": "Additive-model per-allele OR in the confirmed group was 6.00 vs 3.43 in the unconfirmed group and 3.61 combined; misclassification in clinical series dilutes APOE effects." }, { "id": "apoe-e2-allelic-dose-reiman2020", "gene": "APOE", "variant": "APOE e2 allele dose (additive model, e4 non-carriers)", "chromosome": "19", "position_hg38": 44908684, "risk_allele": "e2", "allele_frequency": 0.0794, "allele_frequency_source": "gnomAD genomes non-Finnish European via Ensembl release 116", "effect_size": "OR 0.38 per e2 allele (neuropathologically confirmed group)", "effect_size_type": "odds ratio (genotype comparison as stated)", "odds_ratio": 0.38, "ci_lower": null, "ci_upper": null, "p_value": null, "population": "More than 5,000 clinically and neuropathologically characterized AD dementia cases and controls (ADGC); ORs from logistic regression; predominantly European-ancestry ADGC autopsy series (ancestry composition not stated in abstract)", "ancestry": "European", "study_name": "Reiman et al. 2020, Nat Commun (ADGC neuropathologically confirmed cases and controls)", "n_cases": null, "n_controls": null, "year": 2020, "url": "https://doi.org/10.1038/s41467-019-14279-8", "pubmed_id": "32015339", "classification": "protective", "category": "apoe", "value_type": "measured", "notes": "Confirmed 0.38, unconfirmed 0.64, combined 0.59." }, { "id": "apoe-e4e4-penetrance-fortea2024", "gene": "APOE", "variant": "APOE e4/e4 (homozygosity)", "chromosome": "19", "position_hg38": 44908684, "risk_allele": "e4", "allele_frequency": 0.1379, "allele_frequency_source": "gnomAD genomes non-Finnish European via Ensembl release 116 (rs429358-C)", "effect_size": "Near-full penetrance of AD biology: almost all e4 homozygotes had AD pathology; by age 65 nearly all had abnormal CSF amyloid and 75% positive amyloid PET; symptom onset age 65.1 y", "effect_size_type": "penetrance / biomarker positivity (descriptive)", "odds_ratio": null, "ci_lower": null, "ci_upper": null, "p_value": null, "population": "NACC neuropathology (n = 3,297) and five biomarker cohorts (n = 10,039); predominantly non-Hispanic White cohorts", "ancestry": "European", "study_name": "Fortea et al. 2024, Nat Med", "n_cases": null, "n_controls": null, "year": 2024, "url": "https://doi.org/10.1038/s41591-024-02931-w", "pubmed_id": "38710950", "classification": "high-risk", "category": "apoe", "value_type": "measured", "notes": "Authors argue e4/e4 should be considered a distinct genetic form of AD, with onset predictability resembling autosomal-dominant AD and Down syndrome. Whether this holds outside European-ancestry cohorts is untested (see Belloy 2023 e4/e4 OR 6.49 in Black and 3.62 in Hispanic individuals)." }, { "id": "apoe-e4-modifier-rs10423769-rajabli2022-african", "gene": "APOE (modifier locus 19q13.31, PSG cluster / lncRNA ENSG00000282943)", "variant": "rs10423769", "chromosome": "19", "position_hg38": 43100929, "risk_allele": "A (protective, interacts with e4)", "allele_frequency": 0.1135, "allele_frequency_source": "gnomAD genomes African/African American via Ensembl release 116 (A allele; non-Finnish European A freq 0.0017)", "effect_size": "e4 x rs10423769-A interaction beta -0.54 (SE 0.12, p 7.5e-6); e4/e4 OR falls from 7.2 (no A allele) to 2.1 (>=1 A allele)", "effect_size_type": "interaction beta; genotype-stratified OR", "odds_ratio": null, "ci_lower": null, "ci_upper": null, "p_value": null, "population": "Discovery 1,850 AD / 4,331 cognitively intact African Americans; replication Ibadan (63/648) and Puerto Rican (273/275)", "ancestry": "African", "study_name": "Rajabli et al. 2022, PLoS Genet", "n_cases": 1850, "n_controls": 4331, "year": 2022, "url": "https://doi.org/10.1371/journal.pgen.1009977", "pubmed_id": "35788729", "classification": "protective", "category": "apoe", "value_type": "measured", "notes": "African-ancestry-specific locus ~2 Mb upstream of APOE that reduces the e4 risk; a candidate explanation for the attenuated e4 effect in African-ancestry populations. The A allele is essentially absent in Europeans (gnomAD nfe A = 0.0017), so it cannot be studied in European-only GWAS." }, { "id": "apoe-local-ancestry-blue2019-caribbean-hispanic", "gene": "APOE (local ancestry)", "variant": "African- vs European-derived local ancestry at the APOE locus", "chromosome": "19", "position_hg38": 44908684, "risk_allele": null, "allele_frequency": null, "allele_frequency_source": null, "effect_size": "39% lower odds of AD with African-derived ancestry at APOE vs European-derived, after adjusting for APOE genotype, age and genome-wide ancestry", "effect_size_type": "odds reduction (as stated in abstract)", "odds_ratio": null, "ci_lower": null, "ci_upper": null, "p_value": null, "population": "3,067 Caribbean Hispanics and 3,028 individuals of European descent", "ancestry": "Hispanic", "study_name": "Blue et al. 2019, Alzheimers Dement", "n_cases": null, "n_controls": null, "year": 2019, "url": "https://doi.org/10.1016/j.jalz.2019.07.016", "pubmed_id": "31606368", "classification": "protective", "category": "apoe", "value_type": "measured", "notes": "APOE e2 and e4 effects were significant but 'substantially attenuated' in Caribbean Hispanics vs European-ancestry individuals. odds_ratio left empty because the abstract reports a percentage reduction, not an OR." }, { "id": "apoe3-christchurch-r136s-arboleda2019", "gene": "APOE", "variant": "APOE3 Christchurch (R136S), homozygous", "chromosome": "19", "position_hg38": null, "risk_allele": "R136S (protective)", "allele_frequency": null, "allele_frequency_source": null, "effect_size": "Single PSEN1 E280A carrier homozygous for APOE3ch did not develop MCI until her seventies, ~3 decades after expected onset, despite very high amyloid burden", "effect_size_type": "case report (n = 1)", "odds_ratio": null, "ci_lower": null, "ci_upper": null, "p_value": null, "population": "One member of the Colombian (Antioquia) PSEN1 E280A kindred", "ancestry": "Hispanic", "study_name": "Arboleda-Velasquez et al. 2019, Nat Med", "n_cases": 1, "n_controls": null, "year": 2019, "url": "https://doi.org/10.1038/s41591-019-0611-3", "pubmed_id": "31686034", "classification": "protective", "category": "apoe", "value_type": "measured", "notes": "Anecdotal-level evidence (n = 1) but mechanistically influential; do not use quantitatively." }, { "id": "trem2-rs75932628-jonsson2013", "gene": "TREM2", "variant": "rs75932628", "chromosome": "6", "position_hg38": 41161514, "risk_allele": "T", "allele_frequency": 0.0063, "allele_frequency_source": "study-reported effect-allele frequency (GWAS Catalog GCST001743)", "effect_size": "OR 2.90 (95% CI 2.16-3.91) per T allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 2.9, "ci_lower": 2.16, "ci_upper": 3.91, "p_value": 2e-12, "population": "3,550 European ancestry (Icelandic) cases, 8,888 controls; replication 694 cases/4,375 controls + 1,343 cases/5,352 controls", "ancestry": "European", "study_name": "Jonsson et al. 2013, N Engl J Med (deCODE)", "n_cases": 3550, "n_controls": 8888, "year": 2013, "url": "https://www.ebi.ac.uk/gwas/studies/GCST001743", "pubmed_id": "23150908", "classification": "high-risk", "category": "trem2-rare-coding", "value_type": "measured", "notes": "R47H. Abstract: Iceland discovery OR 2.92 (95% CI 2.09-4.09, P 3.42e-10); combined discovery + replication OR 2.90 (2.16-3.91, P 2.1e-12); control frequency 0.46% in Icelanders >=85 y. Catalog effect-allele frequency 0.0063." }, { "id": "trem2-rs75932628-guerreiro2013", "gene": "TREM2", "variant": "rs75932628", "chromosome": "6", "position_hg38": 41161514, "risk_allele": "T (R47H)", "allele_frequency": 0.0021, "allele_frequency_source": "gnomAD genomes non-Finnish European via Ensembl release 116 (T allele; African 0.0004, East Asian 0)", "effect_size": "OR 5.05 (95% CI 2.77-9.16), P 9.0e-9 (entire series, additive model); OR 4.59 (2.49-8.46) in newly genotyped participants", "effect_size_type": "odds ratio per allele", "odds_ratio": 5.05, "ci_lower": 2.77, "ci_upper": 9.16, "p_value": 9e-09, "population": "Discovery: 1,092 AD / 1,107 controls (sequencing); genotyping 1,887 AD / 4,061 controls; plus imputed GWAS meta-analysis; European-ancestry series", "ancestry": "European", "study_name": "Guerreiro et al. 2013, N Engl J Med", "n_cases": 1887, "n_controls": 4061, "year": 2013, "url": "https://doi.org/10.1056/NEJMoa1211851", "pubmed_id": "23150934", "classification": "high-risk", "category": "trem2-rare-coding", "value_type": "measured", "notes": "Read from PMC3631573 (author manuscript). Early small-sample estimate; later large meta-analyses give OR ~2.4 (Sims 2017, Bellenguez 2022) -- classic winner's-curse shrinkage. n_cases/n_controls give the direct-genotyping series." }, { "id": "trem2-rs75932628-sims2017", "gene": "TREM2", "variant": "rs75932628", "chromosome": "6", "position_hg38": 41161514, "risk_allele": "T", "allele_frequency": 0.0021, "allele_frequency_source": "gnomAD genomes nfe via Ensembl release 116", "effect_size": "OR 2.46 (95% CI 2.06-2.92) per T allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 2.4557426, "ci_lower": 2.06, "ci_upper": 2.92, "p_value": 5e-24, "population": "up to 16,097 European ancestry cases, up to 18,077 European ancestry controls (stage 1); replication up to 20,693 cases, 30,266 controls", "ancestry": "European", "study_name": "Sims et al. 2017, Nat Genet (exome-array, IGAP)", "n_cases": 16097, "n_controls": 18077, "year": 2017, "url": "https://www.ebi.ac.uk/gwas/studies/GCST005549", "pubmed_id": "28714976", "classification": "high-risk", "category": "trem2-rare-coding", "value_type": "measured", "notes": "R47H in the IGAP exome-array study (stage 1). Catalog OR 2.4557 (95% CI 2.06-2.92), P 5e-24." }, { "id": "trem2-rs75932628-bellenguez2022", "gene": "TREM2", "variant": "rs75932628", "chromosome": "6", "position_hg38": 41161514, "risk_allele": "T", "allele_frequency": 0.0031, "allele_frequency_source": "study-reported effect-allele frequency (GWAS Catalog GCST90027158)", "effect_size": "OR 2.39 (95% CI 2.09-2.73) per T allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 2.39, "ci_lower": 2.09, "ci_upper": 2.73, "p_value": 3e-37, "population": "39,106 European ancestry clinically diagnosed cases, 46,828 European ancestry proxy cases, 401,577 European ancestry controls (stage 1); replication 25,392 cases, 276,086 controls", "ancestry": "European", "study_name": "Bellenguez et al. 2022, Nat Genet (EADB/IGAP/UKB stage 1)", "n_cases": 85934, "n_controls": 401577, "year": 2022, "url": "https://www.ebi.ac.uk/gwas/studies/GCST90027158", "pubmed_id": "35379992", "classification": "high-risk", "category": "trem2-rare-coding", "value_type": "measured", "notes": "R47H in the largest European GWAS: OR 2.39 (2.09-2.73), P 3e-37, effect-allele frequency 0.0031. R47H is essentially absent in East Asian and African populations (gnomAD eas 0, afr 0.0004), so TREM2 risk in those populations is carried by other variants." }, { "id": "trem2-rs143332484-sims2017", "gene": "TREM2", "variant": "rs143332484", "chromosome": "6", "position_hg38": 41161469, "risk_allele": "T", "allele_frequency": 0.0107, "allele_frequency_source": "gnomAD genomes nfe via Ensembl release 116", "effect_size": "OR 1.67 (95% CI 1.46-1.90) per T allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 1.6665556, "ci_lower": 1.46, "ci_upper": 1.9, "p_value": 2e-14, "population": "up to 16,097 European ancestry cases, up to 18,077 European ancestry controls (stage 1); replication up to 20,693 cases, 30,266 controls", "ancestry": "European", "study_name": "Sims et al. 2017, Nat Genet (exome-array, IGAP)", "n_cases": 16097, "n_controls": 18077, "year": 2017, "url": "https://www.ebi.ac.uk/gwas/studies/GCST005549", "pubmed_id": "28714976", "classification": "moderate-risk", "category": "trem2-rare-coding", "value_type": "measured", "notes": "R62H (p.Arg62His). Abstract: OR 1.67, P 1.55e-14, MAF cases 0.0143 vs controls 0.0089." }, { "id": "trem2-rs143332484-bellenguez2022", "gene": "TREM2", "variant": "rs143332484", "chromosome": "6", "position_hg38": 41161469, "risk_allele": "T", "allele_frequency": 0.0126, "allele_frequency_source": "study-reported effect-allele frequency (GWAS Catalog GCST90027158)", "effect_size": "OR 1.41 (95% CI 1.32-1.50) per T allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 1.41, "ci_lower": 1.32, "ci_upper": 1.5, "p_value": 3.0000000000000002e-25, "population": "39,106 European ancestry clinically diagnosed cases, 46,828 European ancestry proxy cases, 401,577 European ancestry controls (stage 1); replication 25,392 cases, 276,086 controls", "ancestry": "European", "study_name": "Bellenguez et al. 2022, Nat Genet (EADB/IGAP/UKB stage 1)", "n_cases": 85934, "n_controls": 401577, "year": 2022, "url": "https://www.ebi.ac.uk/gwas/studies/GCST90027158", "pubmed_id": "35379992", "classification": "moderate-risk", "category": "trem2-rare-coding", "value_type": "measured", "notes": "R62H in Bellenguez 2022: OR 1.41 (1.32-1.50), effect-allele frequency 0.0126." }, { "id": "trem2/treml2-rs60755019-bellenguez2022", "gene": "TREM2/TREML2 region", "variant": "rs60755019", "chromosome": "6", "position_hg38": 41181270, "risk_allele": "G", "allele_frequency": 0.00419999999999998, "allele_frequency_source": "study-reported effect-allele frequency (GWAS Catalog GCST90027158)", "effect_size": "OR 1.55 (95% CI 1.33-1.80) per G allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 1.55, "ci_lower": 1.33, "ci_upper": 1.8, "p_value": 2e-08, "population": "39,106 European ancestry clinically diagnosed cases, 46,828 European ancestry proxy cases, 401,577 European ancestry controls (stage 1); replication 25,392 cases, 276,086 controls", "ancestry": "European", "study_name": "Bellenguez et al. 2022, Nat Genet (EADB/IGAP/UKB stage 1)", "n_cases": 85934, "n_controls": 401577, "year": 2022, "url": "https://www.ebi.ac.uk/gwas/studies/GCST90027158", "pubmed_id": "35379992", "classification": "moderate-risk", "category": "trem2-rare-coding", "value_type": "measured", "notes": "Third independent signal at the TREM2 locus in Bellenguez 2022 (OR 1.55, 1.33-1.80; frequency 0.0042)." }, { "id": "trem2-rs2234253-t96k-african-enriched", "gene": "TREM2", "variant": "rs2234253", "chromosome": "6", "position_hg38": 41161367, "risk_allele": "T (T96K)", "allele_frequency": 0.1228, "allele_frequency_source": "gnomAD genomes African/African American via Ensembl release 116 (T allele; non-Finnish European 0.0010, East Asian 0.0002)", "effect_size": "p = 2e-7 in MVP African-ancestry ADRD/proxy meta-analysis (GWAS Catalog GCST90267627; no OR curated); not genome-wide significant", "effect_size_type": "p-value only", "odds_ratio": null, "ci_lower": null, "ci_upper": null, "p_value": 2e-07, "population": "6,796 African American cases, 4,385 African American maternal proxy cases, 2,256 African American paternal proxy cases, 69,627 African American controls", "ancestry": "African", "study_name": "Sherva et al. 2023, Mol Psychiatry (Million Veteran Program African ancestry ADRD + proxy, meta-analysed with ADGC)", "n_cases": 6796, "n_controls": 69627, "year": 2023, "url": "https://www.ebi.ac.uk/gwas/studies/GCST90267627", "pubmed_id": "36543923", "classification": "disputed", "category": "trem2-rare-coding", "value_type": "measured", "notes": "T96K is common in African ancestry (~12% of alleles) and near-absent in Europeans, so it is invisible to European GWAS. Included as a suggestive (p 2e-7) signal only; effect direction/OR were not curated in the catalog record and are not asserted here." }, { "id": "trem2/treml2-rs73427293-sherva2023", "gene": "TREM2/TREML2 region (African-ancestry lead variant)", "variant": "rs73427293", "chromosome": "6", "position_hg38": 41168873, "risk_allele": "A", "allele_frequency": null, "allele_frequency_source": null, "effect_size": "p = 3e-09 (effect size not curated)", "effect_size_type": "p-value only", "odds_ratio": null, "ci_lower": null, "ci_upper": null, "p_value": 3.0000000000000004e-09, "population": "6,796 African American cases, 4,385 African American maternal proxy cases, 2,256 African American paternal proxy cases, 69,627 African American controls", "ancestry": "African", "study_name": "Sherva et al. 2023, Mol Psychiatry (Million Veteran Program African ancestry ADRD + proxy, meta-analysed with ADGC)", "n_cases": 6796, "n_controls": 69627, "year": 2023, "url": "https://www.ebi.ac.uk/gwas/studies/GCST90267627", "pubmed_id": "36543923", "classification": "moderate-risk", "category": "multi-ancestry", "value_type": "measured", "notes": "Abstract: 'MVP/ADGC meta-analysis yielded additional significant SNPs near known AD risk genes TREM2 (rs73427293, p = 2.95e-9)'; the peak variant differs from the European R47H. gnomAD afr frequency of the T allele 0.124, nfe 0.001." }, { "id": "plcg2-rs72824905-sims2017", "gene": "PLCG2", "variant": "rs72824905", "chromosome": "16", "position_hg38": 81908423, "risk_allele": null, "allele_frequency": null, "allele_frequency_source": null, "effect_size": "OR 1.48 (95% CI 1.25-1.67) (effect allele not specified in catalog record; OR may be inverted)", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 1.4756235, "ci_lower": 1.25, "ci_upper": 1.67, "p_value": 5e-10, "population": "up to 16,097 European ancestry cases, up to 18,077 European ancestry controls (stage 1); replication up to 20,693 cases, 30,266 controls", "ancestry": "European", "study_name": "Sims et al. 2017, Nat Genet (exome-array, IGAP)", "n_cases": 16097, "n_controls": 18077, "year": 2017, "url": "https://www.ebi.ac.uk/gwas/studies/GCST005549", "pubmed_id": "28714976", "classification": "protective", "category": "trem2-rare-coding", "value_type": "measured", "notes": "P522R. Abstract: protective, OR 0.68, P 5.38e-10, MAF cases 0.0059 vs controls 0.0093. The catalog stores the inverted OR (1.4756) because the effect allele was not specified; use the abstract value 0.68 for the G (Arg) allele." }, { "id": "plcg2-rs72824905-bellenguez2022", "gene": "PLCG2", "variant": "rs72824905", "chromosome": "16", "position_hg38": 81908423, "risk_allele": "G", "allele_frequency": 0.00780000000000003, "allele_frequency_source": "study-reported effect-allele frequency (GWAS Catalog GCST90027158)", "effect_size": "OR 0.74 (95% CI 0.68-0.81) per G allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 0.74, "ci_lower": 0.68, "ci_upper": 0.81, "p_value": 8e-12, "population": "39,106 European ancestry clinically diagnosed cases, 46,828 European ancestry proxy cases, 401,577 European ancestry controls (stage 1); replication 25,392 cases, 276,086 controls", "ancestry": "European", "study_name": "Bellenguez et al. 2022, Nat Genet (EADB/IGAP/UKB stage 1)", "n_cases": 85934, "n_controls": 401577, "year": 2022, "url": "https://www.ebi.ac.uk/gwas/studies/GCST90027158", "pubmed_id": "35379992", "classification": "protective", "category": "trem2-rare-coding", "value_type": "measured", "notes": "P522R in Bellenguez 2022: OR 0.74 (0.68-0.81) per G allele; frequency 0.0078. Microglial gain-of-function variant; also protective for FTD/DLB in other studies (not loaded)." }, { "id": "abi3-rs616338-sims2017", "gene": "ABI3", "variant": "rs616338", "chromosome": "17", "position_hg38": 49219935, "risk_allele": "T", "allele_frequency": 0.0095, "allele_frequency_source": "gnomAD genomes nfe via Ensembl release 116", "effect_size": "OR 1.43 (95% CI 1.30-1.60) per T allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 1.4296066, "ci_lower": 1.3, "ci_upper": 1.6, "p_value": 5e-10, "population": "up to 16,097 European ancestry cases, up to 18,077 European ancestry controls (stage 1); replication up to 20,693 cases, 30,266 controls", "ancestry": "European", "study_name": "Sims et al. 2017, Nat Genet (exome-array, IGAP)", "n_cases": 16097, "n_controls": 18077, "year": 2017, "url": "https://www.ebi.ac.uk/gwas/studies/GCST005549", "pubmed_id": "28714976", "classification": "moderate-risk", "category": "trem2-rare-coding", "value_type": "measured", "notes": "S209F. Abstract: OR 1.43, P 4.56e-10, MAF cases 0.011 vs controls 0.008." }, { "id": "abi3-rs616338-bellenguez2022", "gene": "ABI3", "variant": "rs616338", "chromosome": "17", "position_hg38": 49219935, "risk_allele": "T", "allele_frequency": 0.0122, "allele_frequency_source": "study-reported effect-allele frequency (GWAS Catalog GCST90027158)", "effect_size": "OR 1.32 (95% CI 1.23-1.42) per T allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 1.32, "ci_lower": 1.23, "ci_upper": 1.42, "p_value": 3e-14, "population": "39,106 European ancestry clinically diagnosed cases, 46,828 European ancestry proxy cases, 401,577 European ancestry controls (stage 1); replication 25,392 cases, 276,086 controls", "ancestry": "European", "study_name": "Bellenguez et al. 2022, Nat Genet (EADB/IGAP/UKB stage 1)", "n_cases": 85934, "n_controls": 401577, "year": 2022, "url": "https://www.ebi.ac.uk/gwas/studies/GCST90027158", "pubmed_id": "35379992", "classification": "moderate-risk", "category": "trem2-rare-coding", "value_type": "measured", "notes": "S209F in Bellenguez 2022: OR 1.32 (1.23-1.42), frequency 0.0122." }, { "id": "cr1-rs679515-bellenguez2022", "gene": "CR1", "variant": "rs679515", "chromosome": "1", "position_hg38": 207577223, "risk_allele": "T", "allele_frequency": 0.1877, "allele_frequency_source": "study-reported effect-allele frequency (GWAS Catalog GCST90027158)", "effect_size": "OR 1.13 (95% CI 1.11-1.15) per T allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 1.13, "ci_lower": 1.11, "ci_upper": 1.15, "p_value": 7e-46, "population": "39,106 European ancestry clinically diagnosed cases, 46,828 European ancestry proxy cases, 401,577 European ancestry controls (stage 1); replication 25,392 cases, 276,086 controls", "ancestry": "European", "study_name": "Bellenguez et al. 2022, Nat Genet (EADB/IGAP/UKB stage 1)", "n_cases": 85934, "n_controls": 401577, "year": 2022, "url": "https://www.ebi.ac.uk/gwas/studies/GCST90027158", "pubmed_id": "35379992", "classification": "low-risk/modifier", "category": "gwas-locus", "value_type": "measured", "notes": "First reported by Lambert 2009; Lambert 2013 lead rs6656401-A OR 1.18 (1.14-1.22). Complement receptor 1." }, { "id": "cr1-rs6656401-lambert2013", "gene": "CR1", "variant": "rs6656401", "chromosome": "1", "position_hg38": 207518704, "risk_allele": "A", "allele_frequency": 0.197, "allele_frequency_source": "study-reported effect-allele frequency (GWAS Catalog GCST002245)", "effect_size": "OR 1.18 (95% CI 1.14-1.22) per A allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 1.18, "ci_lower": 1.14, "ci_upper": 1.22, "p_value": 5.999999999999999e-24, "population": "17,008 European ancestry cases, 37,154 European ancestry controls (stage 1); replication 8,572 cases, 11,312 controls", "ancestry": "European", "study_name": "Lambert et al. 2013, Nat Genet (IGAP stage 1)", "n_cases": 17008, "n_controls": 37154, "year": 2013, "url": "https://www.ebi.ac.uk/gwas/studies/GCST002245", "pubmed_id": "24162737", "classification": "moderate-risk", "category": "gwas-locus", "value_type": "measured", "notes": "Lambert 2013 stage-1 estimate for the original CR1 lead SNP." }, { "id": "bin1-rs6733839-bellenguez2022", "gene": "BIN1", "variant": "rs6733839", "chromosome": "2", "position_hg38": 127135234, "risk_allele": "T", "allele_frequency": 0.3891, "allele_frequency_source": "study-reported effect-allele frequency (GWAS Catalog GCST90027158)", "effect_size": "OR 1.17 (95% CI 1.16-1.19) per T allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 1.17, "ci_lower": 1.16, "ci_upper": 1.19, "p_value": 5.9999999999999995e-118, "population": "39,106 European ancestry clinically diagnosed cases, 46,828 European ancestry proxy cases, 401,577 European ancestry controls (stage 1); replication 25,392 cases, 276,086 controls", "ancestry": "European", "study_name": "Bellenguez et al. 2022, Nat Genet (EADB/IGAP/UKB stage 1)", "n_cases": 85934, "n_controls": 401577, "year": 2022, "url": "https://www.ebi.ac.uk/gwas/studies/GCST90027158", "pubmed_id": "35379992", "classification": "moderate-risk", "category": "gwas-locus", "value_type": "measured", "notes": "Strongest non-APOE common locus (P 6e-118). Lambert 2013: OR 1.22 (1.18-1.25). gnomAD T allele: nfe 0.385, afr 0.396, eas 0.399." }, { "id": "clu-rs11787077-bellenguez2022", "gene": "CLU", "variant": "rs11787077", "chromosome": "8", "position_hg38": 27607795, "risk_allele": "T", "allele_frequency": 0.392, "allele_frequency_source": "study-reported effect-allele frequency (GWAS Catalog GCST90027158)", "effect_size": "OR 0.91 (95% CI 0.90-0.92) per T allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 0.91, "ci_lower": 0.9, "ci_upper": 0.92, "p_value": 2e-44, "population": "39,106 European ancestry clinically diagnosed cases, 46,828 European ancestry proxy cases, 401,577 European ancestry controls (stage 1); replication 25,392 cases, 276,086 controls", "ancestry": "European", "study_name": "Bellenguez et al. 2022, Nat Genet (EADB/IGAP/UKB stage 1)", "n_cases": 85934, "n_controls": 401577, "year": 2022, "url": "https://www.ebi.ac.uk/gwas/studies/GCST90027158", "pubmed_id": "35379992", "classification": "protective", "category": "gwas-locus", "value_type": "measured", "notes": "Effect allele T is protective (OR 0.91). Lambert 2013 lead rs9331896 OR 1.16 for the C allele (catalog stores inverted 1.1628 for T). gnomAD rs9331896-C: nfe 0.403, afr 0.562, eas 0.225 -- the CLU risk allele is far commoner in African and rarer in East Asian populations." }, { "id": "picalm-rs3851179-bellenguez2022", "gene": "PICALM", "variant": "rs3851179", "chromosome": "11", "position_hg38": 86157598, "risk_allele": "T", "allele_frequency": 0.3584, "allele_frequency_source": "study-reported effect-allele frequency (GWAS Catalog GCST90027158)", "effect_size": "OR 0.90 (95% CI 0.89-0.92) per T allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 0.9, "ci_lower": 0.89, "ci_upper": 0.92, "p_value": 3e-48, "population": "39,106 European ancestry clinically diagnosed cases, 46,828 European ancestry proxy cases, 401,577 European ancestry controls (stage 1); replication 25,392 cases, 276,086 controls", "ancestry": "European", "study_name": "Bellenguez et al. 2022, Nat Genet (EADB/IGAP/UKB stage 1)", "n_cases": 85934, "n_controls": 401577, "year": 2022, "url": "https://www.ebi.ac.uk/gwas/studies/GCST90027158", "pubmed_id": "35379992", "classification": "protective", "category": "gwas-locus", "value_type": "measured", "notes": "Effect allele T protective (OR 0.90). Lambert 2013 lead rs10792832. gnomAD rs3851179-T: nfe 0.365, afr 0.155, eas 0.398." }, { "id": "sorl1-rs11218343-bellenguez2022", "gene": "SORL1", "variant": "rs11218343", "chromosome": "11", "position_hg38": 121564878, "risk_allele": "C", "allele_frequency": 0.039, "allele_frequency_source": "study-reported effect-allele frequency (GWAS Catalog GCST90027158)", "effect_size": "OR 0.84 (95% CI 0.81-0.87) per C allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 0.84, "ci_lower": 0.81, "ci_upper": 0.87, "p_value": 1e-21, "population": "39,106 European ancestry clinically diagnosed cases, 46,828 European ancestry proxy cases, 401,577 European ancestry controls (stage 1); replication 25,392 cases, 276,086 controls", "ancestry": "European", "study_name": "Bellenguez et al. 2022, Nat Genet (EADB/IGAP/UKB stage 1)", "n_cases": 85934, "n_controls": 401577, "year": 2022, "url": "https://www.ebi.ac.uk/gwas/studies/GCST90027158", "pubmed_id": "35379992", "classification": "protective", "category": "gwas-locus", "value_type": "measured", "notes": "Effect allele C protective (OR 0.84, freq 0.039). Miyashita 2013 first reached genome-wide significance for SORL1 by combining Japanese, Korean and Caucasian samples (P 1.77e-9); gnomAD rs11218343-C: eas 0.299, nfe 0.039, afr 0.080 -- much commoner in East Asians." }, { "id": "sorl1-rs74685827-bellenguez2022", "gene": "SORL1", "variant": "rs74685827", "chromosome": "11", "position_hg38": 121482368, "risk_allele": "G", "allele_frequency": 0.0185999999999999, "allele_frequency_source": "study-reported effect-allele frequency (GWAS Catalog GCST90027158)", "effect_size": "OR 1.19 (95% CI 1.13-1.25) per G allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 1.19, "ci_lower": 1.13, "ci_upper": 1.25, "p_value": 3e-11, "population": "39,106 European ancestry clinically diagnosed cases, 46,828 European ancestry proxy cases, 401,577 European ancestry controls (stage 1); replication 25,392 cases, 276,086 controls", "ancestry": "European", "study_name": "Bellenguez et al. 2022, Nat Genet (EADB/IGAP/UKB stage 1)", "n_cases": 85934, "n_controls": 401577, "year": 2022, "url": "https://www.ebi.ac.uk/gwas/studies/GCST90027158", "pubmed_id": "35379992", "classification": "moderate-risk", "category": "gwas-locus", "value_type": "measured", "notes": "Second, rare SORL1 signal (OR 1.19, freq 0.0186). Rare SORL1 loss-of-function variants (not loaded here) carry far larger effects." }, { "id": "abca7-rs12151021-bellenguez2022", "gene": "ABCA7", "variant": "rs12151021", "chromosome": "19", "position_hg38": 1050875, "risk_allele": "A", "allele_frequency": 0.3357, "allele_frequency_source": "study-reported effect-allele frequency (GWAS Catalog GCST90027158)", "effect_size": "OR 1.10 (95% CI 1.09-1.12) per A allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 1.1, "ci_lower": 1.09, "ci_upper": 1.12, "p_value": 2e-37, "population": "39,106 European ancestry clinically diagnosed cases, 46,828 European ancestry proxy cases, 401,577 European ancestry controls (stage 1); replication 25,392 cases, 276,086 controls", "ancestry": "European", "study_name": "Bellenguez et al. 2022, Nat Genet (EADB/IGAP/UKB stage 1)", "n_cases": 85934, "n_controls": 401577, "year": 2022, "url": "https://www.ebi.ac.uk/gwas/studies/GCST90027158", "pubmed_id": "35379992", "classification": "low-risk/modifier", "category": "gwas-locus", "value_type": "measured", "notes": "European ABCA7 lead. In African Americans the lead is a different, higher-frequency variant rs115550680 with OR 1.79 (Reitz 2013), see separate record." }, { "id": "abca7-rs4147929-lambert2013", "gene": "ABCA7", "variant": "rs4147929", "chromosome": "19", "position_hg38": 1063444, "risk_allele": "A", "allele_frequency": 0.19, "allele_frequency_source": "study-reported effect-allele frequency (GWAS Catalog GCST002245)", "effect_size": "OR 1.15 (95% CI 1.11-1.19) per A allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 1.15, "ci_lower": 1.11, "ci_upper": 1.19, "p_value": 1e-15, "population": "17,008 European ancestry cases, 37,154 European ancestry controls (stage 1); replication 8,572 cases, 11,312 controls", "ancestry": "European", "study_name": "Lambert et al. 2013, Nat Genet (IGAP stage 1)", "n_cases": 17008, "n_controls": 37154, "year": 2013, "url": "https://www.ebi.ac.uk/gwas/studies/GCST002245", "pubmed_id": "24162737", "classification": "moderate-risk", "category": "gwas-locus", "value_type": "measured", "notes": "Lambert 2013 stage-1 ABCA7 lead. gnomAD rs4147929-A: nfe 0.172, afr 0.043, eas 0.335." }, { "id": "ms4a4a/ms4a6a-rs1582763-bellenguez2022", "gene": "MS4A4A/MS4A6A cluster", "variant": "rs1582763", "chromosome": "11", "position_hg38": 60254475, "risk_allele": "A", "allele_frequency": 0.371, "allele_frequency_source": "study-reported effect-allele frequency (GWAS Catalog GCST90027158)", "effect_size": "OR 0.91 (95% CI 0.90-0.92) per A allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 0.91, "ci_lower": 0.9, "ci_upper": 0.92, "p_value": 4e-42, "population": "39,106 European ancestry clinically diagnosed cases, 46,828 European ancestry proxy cases, 401,577 European ancestry controls (stage 1); replication 25,392 cases, 276,086 controls", "ancestry": "European", "study_name": "Bellenguez et al. 2022, Nat Genet (EADB/IGAP/UKB stage 1)", "n_cases": 85934, "n_controls": 401577, "year": 2022, "url": "https://www.ebi.ac.uk/gwas/studies/GCST90027158", "pubmed_id": "35379992", "classification": "protective", "category": "gwas-locus", "value_type": "measured", "notes": "MS4A gene cluster (chr11q12); effect allele A protective (OR 0.91). Lambert 2013 lead rs983392 (MS4A6A) OR 1.11 for the A allele. gnomAD rs983392-G: nfe 0.411, afr 0.078, eas 0.057." }, { "id": "ms4a6a-rs983392-lambert2013", "gene": "MS4A6A", "variant": "rs983392", "chromosome": "11", "position_hg38": 60156035, "risk_allele": "A", "allele_frequency": 0.597, "allele_frequency_source": "study-reported effect-allele frequency (GWAS Catalog GCST002245)", "effect_size": "OR 1.11 (95% CI 1.09-1.15) per A allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 1.1111, "ci_lower": 1.09, "ci_upper": 1.15, "p_value": 6e-16, "population": "17,008 European ancestry cases, 37,154 European ancestry controls (stage 1); replication 8,572 cases, 11,312 controls", "ancestry": "European", "study_name": "Lambert et al. 2013, Nat Genet (IGAP stage 1)", "n_cases": 17008, "n_controls": 37154, "year": 2013, "url": "https://www.ebi.ac.uk/gwas/studies/GCST002245", "pubmed_id": "24162737", "classification": "low-risk/modifier", "category": "gwas-locus", "value_type": "measured", "notes": "Lambert 2013 stage-1 MS4A6A lead (catalog stores OR 1.1111 for the A allele)." }, { "id": "cd33-rs3865444-lambert2013", "gene": "CD33", "variant": "rs3865444", "chromosome": "19", "position_hg38": 51224706, "risk_allele": "C", "allele_frequency": 0.693, "allele_frequency_source": "study-reported effect-allele frequency (GWAS Catalog GCST002245)", "effect_size": "OR 1.06 (95% CI 1.04-1.10) per C allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 1.06, "ci_lower": 1.04, "ci_upper": 1.1, "p_value": 3e-06, "population": "17,008 European ancestry cases, 37,154 European ancestry controls (stage 1); replication 8,572 cases, 11,312 controls", "ancestry": "European", "study_name": "Lambert et al. 2013, Nat Genet (IGAP stage 1)", "n_cases": 17008, "n_controls": 37154, "year": 2013, "url": "https://www.ebi.ac.uk/gwas/studies/GCST002245", "pubmed_id": "24162737", "classification": "low-risk/modifier", "category": "gwas-locus", "value_type": "measured", "notes": "CD33: Lambert 2013 stage-1 P 3e-6 (not genome-wide significant in stage 1 alone; reached significance in combined stages in earlier IGAP/Naj-Hollingworth 2011 reports). Wightman 2021 rs1354106 P 2e-10 and Jansen 2019 rs3865444 P 6e-9 (z-score) support the locus; Bellenguez 2022 did not list a CD33 lead among catalog-curated associations. gnomAD rs3865444-A: nfe 0.316, afr 0.087, eas 0.188." }, { "id": "cd2ap-rs7767350-bellenguez2022", "gene": "CD2AP", "variant": "rs7767350", "chromosome": "6", "position_hg38": 47517390, "risk_allele": "T", "allele_frequency": 0.2709, "allele_frequency_source": "study-reported effect-allele frequency (GWAS Catalog GCST90027158)", "effect_size": "OR 1.08 (95% CI 1.06-1.09) per T allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 1.08, "ci_lower": 1.06, "ci_upper": 1.09, "p_value": 8e-22, "population": "39,106 European ancestry clinically diagnosed cases, 46,828 European ancestry proxy cases, 401,577 European ancestry controls (stage 1); replication 25,392 cases, 276,086 controls", "ancestry": "European", "study_name": "Bellenguez et al. 2022, Nat Genet (EADB/IGAP/UKB stage 1)", "n_cases": 85934, "n_controls": 401577, "year": 2022, "url": "https://www.ebi.ac.uk/gwas/studies/GCST90027158", "pubmed_id": "35379992", "classification": "low-risk/modifier", "category": "gwas-locus", "value_type": "measured", "notes": "Known locus; also genome-wide significant in African-ancestry MVP (different lead rs7738720, Sherva 2023)." }, { "id": "ptk2b-rs73223431-bellenguez2022", "gene": "PTK2B", "variant": "rs73223431", "chromosome": "8", "position_hg38": 27362470, "risk_allele": "T", "allele_frequency": 0.3694, "allele_frequency_source": "study-reported effect-allele frequency (GWAS Catalog GCST90027158)", "effect_size": "OR 1.07 (95% CI 1.06-1.08) per T allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 1.07, "ci_lower": 1.06, "ci_upper": 1.08, "p_value": 4e-22, "population": "39,106 European ancestry clinically diagnosed cases, 46,828 European ancestry proxy cases, 401,577 European ancestry controls (stage 1); replication 25,392 cases, 276,086 controls", "ancestry": "European", "study_name": "Bellenguez et al. 2022, Nat Genet (EADB/IGAP/UKB stage 1)", "n_cases": 85934, "n_controls": 401577, "year": 2022, "url": "https://www.ebi.ac.uk/gwas/studies/GCST90027158", "pubmed_id": "35379992", "classification": "low-risk/modifier", "category": "gwas-locus", "value_type": "measured", "notes": "" }, { "id": "epha1-rs11771145-bellenguez2022", "gene": "EPHA1", "variant": "rs11771145", "chromosome": "7", "position_hg38": 143413669, "risk_allele": "A", "allele_frequency": 0.3476, "allele_frequency_source": "study-reported effect-allele frequency (GWAS Catalog GCST90027158)", "effect_size": "OR 0.95 (95% CI 0.93-0.96) per A allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 0.95, "ci_lower": 0.93, "ci_upper": 0.96, "p_value": 3e-14, "population": "39,106 European ancestry clinically diagnosed cases, 46,828 European ancestry proxy cases, 401,577 European ancestry controls (stage 1); replication 25,392 cases, 276,086 controls", "ancestry": "European", "study_name": "Bellenguez et al. 2022, Nat Genet (EADB/IGAP/UKB stage 1)", "n_cases": 85934, "n_controls": 401577, "year": 2022, "url": "https://www.ebi.ac.uk/gwas/studies/GCST90027158", "pubmed_id": "35379992", "classification": "protective", "category": "gwas-locus", "value_type": "measured", "notes": "Effect allele A protective." }, { "id": "inpp5d-rs10933431-bellenguez2022", "gene": "INPP5D", "variant": "rs10933431", "chromosome": "2", "position_hg38": 233117202, "risk_allele": "G", "allele_frequency": 0.2343, "allele_frequency_source": "study-reported effect-allele frequency (GWAS Catalog GCST90027158)", "effect_size": "OR 0.93 (95% CI 0.92-0.95) per G allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 0.93, "ci_lower": 0.92, "ci_upper": 0.95, "p_value": 4e-18, "population": "39,106 European ancestry clinically diagnosed cases, 46,828 European ancestry proxy cases, 401,577 European ancestry controls (stage 1); replication 25,392 cases, 276,086 controls", "ancestry": "European", "study_name": "Bellenguez et al. 2022, Nat Genet (EADB/IGAP/UKB stage 1)", "n_cases": 85934, "n_controls": 401577, "year": 2022, "url": "https://www.ebi.ac.uk/gwas/studies/GCST90027158", "pubmed_id": "35379992", "classification": "protective", "category": "gwas-locus", "value_type": "measured", "notes": "Effect allele G protective." }, { "id": "fermt2-rs17125924-bellenguez2022", "gene": "FERMT2", "variant": "rs17125924", "chromosome": "14", "position_hg38": 52924962, "risk_allele": "G", "allele_frequency": 0.0891999999999999, "allele_frequency_source": "study-reported effect-allele frequency (GWAS Catalog GCST90027158)", "effect_size": "OR 1.10 (95% CI 1.07-1.12) per G allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 1.1, "ci_lower": 1.07, "ci_upper": 1.12, "p_value": 8e-16, "population": "39,106 European ancestry clinically diagnosed cases, 46,828 European ancestry proxy cases, 401,577 European ancestry controls (stage 1); replication 25,392 cases, 276,086 controls", "ancestry": "European", "study_name": "Bellenguez et al. 2022, Nat Genet (EADB/IGAP/UKB stage 1)", "n_cases": 85934, "n_controls": 401577, "year": 2022, "url": "https://www.ebi.ac.uk/gwas/studies/GCST90027158", "pubmed_id": "35379992", "classification": "low-risk/modifier", "category": "gwas-locus", "value_type": "measured", "notes": "" }, { "id": "slc24a4/rin3-rs12590654-bellenguez2022", "gene": "SLC24A4/RIN3", "variant": "rs12590654", "chromosome": "14", "position_hg38": 92472511, "risk_allele": "A", "allele_frequency": 0.3279, "allele_frequency_source": "study-reported effect-allele frequency (GWAS Catalog GCST90027158)", "effect_size": "OR 0.93 (95% CI 0.92-0.95) per A allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 0.93, "ci_lower": 0.92, "ci_upper": 0.95, "p_value": 4e-21, "population": "39,106 European ancestry clinically diagnosed cases, 46,828 European ancestry proxy cases, 401,577 European ancestry controls (stage 1); replication 25,392 cases, 276,086 controls", "ancestry": "European", "study_name": "Bellenguez et al. 2022, Nat Genet (EADB/IGAP/UKB stage 1)", "n_cases": 85934, "n_controls": 401577, "year": 2022, "url": "https://www.ebi.ac.uk/gwas/studies/GCST90027158", "pubmed_id": "35379992", "classification": "protective", "category": "gwas-locus", "value_type": "measured", "notes": "Effect allele A protective." }, { "id": "cass4-rs6014724-bellenguez2022", "gene": "CASS4", "variant": "rs6014724", "chromosome": "20", "position_hg38": 56423488, "risk_allele": "G", "allele_frequency": 0.0898, "allele_frequency_source": "study-reported effect-allele frequency (GWAS Catalog GCST90027158)", "effect_size": "OR 0.89 (95% CI 0.87-0.91) per G allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 0.89, "ci_lower": 0.87, "ci_upper": 0.91, "p_value": 4e-21, "population": "39,106 European ancestry clinically diagnosed cases, 46,828 European ancestry proxy cases, 401,577 European ancestry controls (stage 1); replication 25,392 cases, 276,086 controls", "ancestry": "European", "study_name": "Bellenguez et al. 2022, Nat Genet (EADB/IGAP/UKB stage 1)", "n_cases": 85934, "n_controls": 401577, "year": 2022, "url": "https://www.ebi.ac.uk/gwas/studies/GCST90027158", "pubmed_id": "35379992", "classification": "protective", "category": "gwas-locus", "value_type": "measured", "notes": "Effect allele G protective." }, { "id": "hla-dqa1/hla-drb1-rs6605556-bellenguez2022", "gene": "HLA-DQA1/HLA-DRB1", "variant": "rs6605556", "chromosome": "6", "position_hg38": 32615322, "risk_allele": "G", "allele_frequency": 0.1613, "allele_frequency_source": "study-reported effect-allele frequency (GWAS Catalog GCST90027158)", "effect_size": "OR 0.91 (95% CI 0.90-0.93) per G allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 0.91, "ci_lower": 0.9, "ci_upper": 0.93, "p_value": 7e-20, "population": "39,106 European ancestry clinically diagnosed cases, 46,828 European ancestry proxy cases, 401,577 European ancestry controls (stage 1); replication 25,392 cases, 276,086 controls", "ancestry": "European", "study_name": "Bellenguez et al. 2022, Nat Genet (EADB/IGAP/UKB stage 1)", "n_cases": 85934, "n_controls": 401577, "year": 2022, "url": "https://www.ebi.ac.uk/gwas/studies/GCST90027158", "pubmed_id": "35379992", "classification": "protective", "category": "gwas-locus", "value_type": "measured", "notes": "HLA class II; Kunkle 2019 fine-mapping implicated the HLA-DR15 haplotype." }, { "id": "aph1b-rs117618017-bellenguez2022", "gene": "APH1B", "variant": "rs117618017", "chromosome": "15", "position_hg38": 63277703, "risk_allele": "T", "allele_frequency": 0.1439, "allele_frequency_source": "study-reported effect-allele frequency (GWAS Catalog GCST90027158)", "effect_size": "OR 1.11 (95% CI 1.09-1.13) per T allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 1.11, "ci_lower": 1.09, "ci_upper": 1.13, "p_value": 2e-25, "population": "39,106 European ancestry clinically diagnosed cases, 46,828 European ancestry proxy cases, 401,577 European ancestry controls (stage 1); replication 25,392 cases, 276,086 controls", "ancestry": "European", "study_name": "Bellenguez et al. 2022, Nat Genet (EADB/IGAP/UKB stage 1)", "n_cases": 85934, "n_controls": 401577, "year": 2022, "url": "https://www.ebi.ac.uk/gwas/studies/GCST90027158", "pubmed_id": "35379992", "classification": "low-risk/modifier", "category": "gwas-locus", "value_type": "measured", "notes": "Gamma-secretase component; missense variant." }, { "id": "spi1-rs10437655-bellenguez2022", "gene": "SPI1", "variant": "rs10437655", "chromosome": "11", "position_hg38": 47370397, "risk_allele": "A", "allele_frequency": 0.3987, "allele_frequency_source": "study-reported effect-allele frequency (GWAS Catalog GCST90027158)", "effect_size": "OR 1.06 (95% CI 1.04-1.07) per A allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 1.06, "ci_lower": 1.04, "ci_upper": 1.07, "p_value": 5e-14, "population": "39,106 European ancestry clinically diagnosed cases, 46,828 European ancestry proxy cases, 401,577 European ancestry controls (stage 1); replication 25,392 cases, 276,086 controls", "ancestry": "European", "study_name": "Bellenguez et al. 2022, Nat Genet (EADB/IGAP/UKB stage 1)", "n_cases": 85934, "n_controls": 401577, "year": 2022, "url": "https://www.ebi.ac.uk/gwas/studies/GCST90027158", "pubmed_id": "35379992", "classification": "low-risk/modifier", "category": "gwas-locus", "value_type": "measured", "notes": "PU.1 transcription factor (microglia)." }, { "id": "adam10-rs593742-kunkle2019", "gene": "ADAM10", "variant": "rs593742", "chromosome": "15", "position_hg38": 58753575, "risk_allele": "A", "allele_frequency": 0.7050000000000001, "allele_frequency_source": "study-reported effect-allele frequency (GWAS Catalog GCST007511)", "effect_size": "OR 1.08 (95% CI 1.05-1.10) per A allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 1.0752687, "ci_lower": 1.05, "ci_upper": 1.1, "p_value": 7.000000000000001e-09, "population": "21,982 European ancestry cases, 41,944 European ancestry controls (stage 1); replication up to 13,292 cases, 17,219 controls", "ancestry": "European", "study_name": "Kunkle et al. 2019, Nat Genet (IGAP stage 1)", "n_cases": 21982, "n_controls": 41944, "year": 2019, "url": "https://www.ebi.ac.uk/gwas/studies/GCST007511", "pubmed_id": "30820047", "classification": "low-risk/modifier", "category": "gwas-locus", "value_type": "measured", "notes": "New locus in Kunkle 2019 (OR curated as 1.0753 for the A allele, P 7e-9); alpha-secretase." }, { "id": "app-rs2154481-bellenguez2022", "gene": "APP", "variant": "rs2154481", "chromosome": "21", "position_hg38": 26101558, "risk_allele": "C", "allele_frequency": 0.4764, "allele_frequency_source": "study-reported effect-allele frequency (GWAS Catalog GCST90027158)", "effect_size": "OR 0.95 (95% CI 0.94-0.97) per C allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 0.95, "ci_lower": 0.94, "ci_upper": 0.97, "p_value": 1e-12, "population": "39,106 European ancestry clinically diagnosed cases, 46,828 European ancestry proxy cases, 401,577 European ancestry controls (stage 1); replication 25,392 cases, 276,086 controls", "ancestry": "European", "study_name": "Bellenguez et al. 2022, Nat Genet (EADB/IGAP/UKB stage 1)", "n_cases": 85934, "n_controls": 401577, "year": 2022, "url": "https://www.ebi.ac.uk/gwas/studies/GCST90027158", "pubmed_id": "35379992", "classification": "protective", "category": "gwas-locus", "value_type": "measured", "notes": "Common protective variant at APP itself (OR 0.95); the same gene carries causal autosomal-dominant mutations (see causal records)." }, { "id": "sort1-rs141749679-bellenguez2022", "gene": "SORT1", "variant": "rs141749679", "chromosome": "1", "position_hg38": 109345810, "risk_allele": "C", "allele_frequency": 0.00380000000000003, "allele_frequency_source": "study-reported effect-allele frequency (GWAS Catalog GCST90027158)", "effect_size": "OR 1.38 (95% CI 1.24-1.54) per C allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 1.38, "ci_lower": 1.24, "ci_upper": 1.54, "p_value": 8e-09, "population": "39,106 European ancestry clinically diagnosed cases, 46,828 European ancestry proxy cases, 401,577 European ancestry controls (stage 1); replication 25,392 cases, 276,086 controls", "ancestry": "European", "study_name": "Bellenguez et al. 2022, Nat Genet (EADB/IGAP/UKB stage 1)", "n_cases": 85934, "n_controls": 401577, "year": 2022, "url": "https://www.ebi.ac.uk/gwas/studies/GCST90027158", "pubmed_id": "35379992", "classification": "moderate-risk", "category": "gwas-locus", "value_type": "measured", "notes": "New in Bellenguez 2022; rare (freq 0.0038), OR 1.38 (1.24-1.54)." }, { "id": "nck2-rs143080277-bellenguez2022", "gene": "NCK2", "variant": "rs143080277", "chromosome": "2", "position_hg38": 105749599, "risk_allele": "C", "allele_frequency": 0.00509999999999999, "allele_frequency_source": "study-reported effect-allele frequency (GWAS Catalog GCST90027158)", "effect_size": "OR 1.47 (95% CI 1.33-1.63) per C allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 1.47, "ci_lower": 1.33, "ci_upper": 1.63, "p_value": 2e-13, "population": "39,106 European ancestry clinically diagnosed cases, 46,828 European ancestry proxy cases, 401,577 European ancestry controls (stage 1); replication 25,392 cases, 276,086 controls", "ancestry": "European", "study_name": "Bellenguez et al. 2022, Nat Genet (EADB/IGAP/UKB stage 1)", "n_cases": 85934, "n_controls": 401577, "year": 2022, "url": "https://www.ebi.ac.uk/gwas/studies/GCST90027158", "pubmed_id": "35379992", "classification": "moderate-risk", "category": "gwas-locus", "value_type": "measured", "notes": "New in Bellenguez 2022; rare (freq 0.0051), OR 1.47 (1.33-1.63)." }, { "id": "sharpin-rs34173062-bellenguez2022", "gene": "SHARPIN", "variant": "rs34173062", "chromosome": "8", "position_hg38": 144103704, "risk_allele": "A", "allele_frequency": 0.0814, "allele_frequency_source": "study-reported effect-allele frequency (GWAS Catalog GCST90027158)", "effect_size": "OR 1.13 (95% CI 1.09-1.16) per A allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 1.13, "ci_lower": 1.09, "ci_upper": 1.16, "p_value": 2e-16, "population": "39,106 European ancestry clinically diagnosed cases, 46,828 European ancestry proxy cases, 401,577 European ancestry controls (stage 1); replication 25,392 cases, 276,086 controls", "ancestry": "European", "study_name": "Bellenguez et al. 2022, Nat Genet (EADB/IGAP/UKB stage 1)", "n_cases": 85934, "n_controls": 401577, "year": 2022, "url": "https://www.ebi.ac.uk/gwas/studies/GCST90027158", "pubmed_id": "35379992", "classification": "low-risk/modifier", "category": "gwas-locus", "value_type": "measured", "notes": "Missense; linear ubiquitin chain assembly complex / TNF-alpha pathway highlighted by Bellenguez 2022. Also genome-wide significant cross-ancestry in Rajabli 2025 with 13.7% of the sample size." }, { "id": "grn-rs5848-bellenguez2022", "gene": "GRN", "variant": "rs5848", "chromosome": "17", "position_hg38": 44352876, "risk_allele": "T", "allele_frequency": 0.2886, "allele_frequency_source": "study-reported effect-allele frequency (GWAS Catalog GCST90027158)", "effect_size": "OR 1.07 (95% CI 1.06-1.09) per T allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 1.07, "ci_lower": 1.06, "ci_upper": 1.09, "p_value": 2e-20, "population": "39,106 European ancestry clinically diagnosed cases, 46,828 European ancestry proxy cases, 401,577 European ancestry controls (stage 1); replication 25,392 cases, 276,086 controls", "ancestry": "European", "study_name": "Bellenguez et al. 2022, Nat Genet (EADB/IGAP/UKB stage 1)", "n_cases": 85934, "n_controls": 401577, "year": 2022, "url": "https://www.ebi.ac.uk/gwas/studies/GCST90027158", "pubmed_id": "35379992", "classification": "low-risk/modifier", "category": "gwas-locus", "value_type": "measured", "notes": "Progranulin 3'UTR variant shared with FTLD-TDP risk; note the Bellenguez phenotype includes proxy 'AD and related dementias'." }, { "id": "tmem106b-rs13237518-bellenguez2022", "gene": "TMEM106B", "variant": "rs13237518", "chromosome": "7", "position_hg38": 12229967, "risk_allele": "A", "allele_frequency": 0.4115, "allele_frequency_source": "study-reported effect-allele frequency (GWAS Catalog GCST90027158)", "effect_size": "OR 0.96 (95% CI 0.94-0.97) per A allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 0.96, "ci_lower": 0.94, "ci_upper": 0.97, "p_value": 4.9999999999999995e-11, "population": "39,106 European ancestry clinically diagnosed cases, 46,828 European ancestry proxy cases, 401,577 European ancestry controls (stage 1); replication 25,392 cases, 276,086 controls", "ancestry": "European", "study_name": "Bellenguez et al. 2022, Nat Genet (EADB/IGAP/UKB stage 1)", "n_cases": 85934, "n_controls": 401577, "year": 2022, "url": "https://www.ebi.ac.uk/gwas/studies/GCST90027158", "pubmed_id": "35379992", "classification": "protective", "category": "gwas-locus", "value_type": "measured", "notes": "FTLD-TDP risk gene; effect allele A protective. Shared with proxy-dementia phenotype." }, { "id": "abca1-rs1800978-bellenguez2022", "gene": "ABCA1", "variant": "rs1800978", "chromosome": "9", "position_hg38": 104903697, "risk_allele": "G", "allele_frequency": 0.13, "allele_frequency_source": "study-reported effect-allele frequency (GWAS Catalog GCST90027158)", "effect_size": "OR 1.06 (95% CI 1.04-1.08) per G allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 1.06, "ci_lower": 1.04, "ci_upper": 1.08, "p_value": 2e-09, "population": "39,106 European ancestry clinically diagnosed cases, 46,828 European ancestry proxy cases, 401,577 European ancestry controls (stage 1); replication 25,392 cases, 276,086 controls", "ancestry": "European", "study_name": "Bellenguez et al. 2022, Nat Genet (EADB/IGAP/UKB stage 1)", "n_cases": 85934, "n_controls": 401577, "year": 2022, "url": "https://www.ebi.ac.uk/gwas/studies/GCST90027158", "pubmed_id": "35379992", "classification": "low-risk/modifier", "category": "gwas-locus", "value_type": "measured", "notes": "New in Bellenguez 2022; cholesterol efflux." }, { "id": "idua-rs3822030-bellenguez2022", "gene": "IDUA", "variant": "rs3822030", "chromosome": "4", "position_hg38": 993555, "risk_allele": "G", "allele_frequency": 0.4288, "allele_frequency_source": "study-reported effect-allele frequency (GWAS Catalog GCST90027158)", "effect_size": "OR 0.95 (95% CI 0.94-0.96) per G allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 0.95, "ci_lower": 0.94, "ci_upper": 0.96, "p_value": 8e-12, "population": "39,106 European ancestry clinically diagnosed cases, 46,828 European ancestry proxy cases, 401,577 European ancestry controls (stage 1); replication 25,392 cases, 276,086 controls", "ancestry": "European", "study_name": "Bellenguez et al. 2022, Nat Genet (EADB/IGAP/UKB stage 1)", "n_cases": 85934, "n_controls": 401577, "year": 2022, "url": "https://www.ebi.ac.uk/gwas/studies/GCST90027158", "pubmed_id": "35379992", "classification": "protective", "category": "gwas-locus", "value_type": "measured", "notes": "New in Bellenguez 2022; effect allele G protective." }, { "id": "atp8b4-rs138799625-bellenguez2022", "gene": "ATP8B4", "variant": "rs138799625", "chromosome": "15", "position_hg38": 49972642, "risk_allele": "T", "allele_frequency": 0.0091, "allele_frequency_source": "study-reported effect-allele frequency (GWAS Catalog GCST90027158)", "effect_size": "OR 1.28 (95% CI 1.18-1.39) per T allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 1.28, "ci_lower": 1.18, "ci_upper": 1.39, "p_value": 1e-09, "population": "39,106 European ancestry clinically diagnosed cases, 46,828 European ancestry proxy cases, 401,577 European ancestry controls (stage 1); replication 25,392 cases, 276,086 controls", "ancestry": "European", "study_name": "Bellenguez et al. 2022, Nat Genet (EADB/IGAP/UKB stage 1)", "n_cases": 85934, "n_controls": 401577, "year": 2022, "url": "https://www.ebi.ac.uk/gwas/studies/GCST90027158", "pubmed_id": "35379992", "classification": "moderate-risk", "category": "gwas-locus", "value_type": "measured", "notes": "New in Bellenguez 2022; rare (freq 0.0091), OR 1.28." }, { "id": "mme-rs61762319-bellenguez2022", "gene": "MME", "variant": "rs61762319", "chromosome": "3", "position_hg38": 155084189, "risk_allele": "G", "allele_frequency": 0.0263, "allele_frequency_source": "study-reported effect-allele frequency (GWAS Catalog GCST90027158)", "effect_size": "OR 1.16 (95% CI 1.11-1.21) per G allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 1.16, "ci_lower": 1.11, "ci_upper": 1.21, "p_value": 2e-11, "population": "39,106 European ancestry clinically diagnosed cases, 46,828 European ancestry proxy cases, 401,577 European ancestry controls (stage 1); replication 25,392 cases, 276,086 controls", "ancestry": "European", "study_name": "Bellenguez et al. 2022, Nat Genet (EADB/IGAP/UKB stage 1)", "n_cases": 85934, "n_controls": 401577, "year": 2022, "url": "https://www.ebi.ac.uk/gwas/studies/GCST90027158", "pubmed_id": "35379992", "classification": "moderate-risk", "category": "gwas-locus", "value_type": "measured", "notes": "New in Bellenguez 2022 (neprilysin, amyloid-degrading enzyme); OR 1.16 (1.11-1.21), freq 0.026." }, { "id": "setd7/qki-rs535347112-bellenguez2022", "gene": "SETD7/QKI region", "variant": "rs535347112", "chromosome": "4", "position_hg38": 139594965, "risk_allele": "T", "allele_frequency": 0.0013, "allele_frequency_source": "study-reported effect-allele frequency (GWAS Catalog GCST90027158)", "effect_size": "OR 2.02 (95% CI 1.57-2.60) per T allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 2.02, "ci_lower": 1.57, "ci_upper": 2.6, "p_value": 4e-08, "population": "39,106 European ancestry clinically diagnosed cases, 46,828 European ancestry proxy cases, 401,577 European ancestry controls (stage 1); replication 25,392 cases, 276,086 controls", "ancestry": "European", "study_name": "Bellenguez et al. 2022, Nat Genet (EADB/IGAP/UKB stage 1)", "n_cases": 85934, "n_controls": 401577, "year": 2022, "url": "https://www.ebi.ac.uk/gwas/studies/GCST90027158", "pubmed_id": "35379992", "classification": "moderate-risk", "category": "gwas-locus", "value_type": "measured", "notes": "Rarest and largest-effect common-GWAS hit in Bellenguez 2022 (freq 0.0013, OR 2.02, 95% CI 1.57-2.60, P 4e-8) -- borderline significance, treat with caution." }, { "id": "tnip1-rs871269-bellenguez2022", "gene": "TNIP1", "variant": "rs871269", "chromosome": "5", "position_hg38": 151052827, "risk_allele": "T", "allele_frequency": 0.3264, "allele_frequency_source": "study-reported effect-allele frequency (GWAS Catalog GCST90027158)", "effect_size": "OR 0.96 (95% CI 0.95-0.97) per T allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 0.96, "ci_lower": 0.95, "ci_upper": 0.97, "p_value": 9.000000000000001e-09, "population": "39,106 European ancestry clinically diagnosed cases, 46,828 European ancestry proxy cases, 401,577 European ancestry controls (stage 1); replication 25,392 cases, 276,086 controls", "ancestry": "European", "study_name": "Bellenguez et al. 2022, Nat Genet (EADB/IGAP/UKB stage 1)", "n_cases": 85934, "n_controls": 401577, "year": 2022, "url": "https://www.ebi.ac.uk/gwas/studies/GCST90027158", "pubmed_id": "35379992", "classification": "protective", "category": "gwas-locus", "value_type": "measured", "notes": "New in Bellenguez 2022; effect allele T protective." }, { "id": "echdc3/usp6nl-rs7912495-bellenguez2022", "gene": "ECHDC3/USP6NL", "variant": "rs7912495", "chromosome": "10", "position_hg38": 11676714, "risk_allele": "G", "allele_frequency": 0.4619, "allele_frequency_source": "study-reported effect-allele frequency (GWAS Catalog GCST90027158)", "effect_size": "OR 1.06 (95% CI 1.05-1.08) per G allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 1.06, "ci_lower": 1.05, "ci_upper": 1.08, "p_value": 1e-18, "population": "39,106 European ancestry clinically diagnosed cases, 46,828 European ancestry proxy cases, 401,577 European ancestry controls (stage 1); replication 25,392 cases, 276,086 controls", "ancestry": "European", "study_name": "Bellenguez et al. 2022, Nat Genet (EADB/IGAP/UKB stage 1)", "n_cases": 85934, "n_controls": 401577, "year": 2022, "url": "https://www.ebi.ac.uk/gwas/studies/GCST90027158", "pubmed_id": "35379992", "classification": "low-risk/modifier", "category": "gwas-locus", "value_type": "measured", "notes": "" }, { "id": "il34-rs4985556-bellenguez2022", "gene": "IL34", "variant": "rs4985556", "chromosome": "16", "position_hg38": 70660097, "risk_allele": "A", "allele_frequency": 0.1148, "allele_frequency_source": "study-reported effect-allele frequency (GWAS Catalog GCST90027158)", "effect_size": "OR 1.07 (95% CI 1.05-1.09) per A allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 1.07, "ci_lower": 1.05, "ci_upper": 1.09, "p_value": 6e-10, "population": "39,106 European ancestry clinically diagnosed cases, 46,828 European ancestry proxy cases, 401,577 European ancestry controls (stage 1); replication 25,392 cases, 276,086 controls", "ancestry": "European", "study_name": "Bellenguez et al. 2022, Nat Genet (EADB/IGAP/UKB stage 1)", "n_cases": 85934, "n_controls": 401577, "year": 2022, "url": "https://www.ebi.ac.uk/gwas/studies/GCST90027158", "pubmed_id": "35379992", "classification": "low-risk/modifier", "category": "gwas-locus", "value_type": "measured", "notes": "Microglial survival cytokine; missense." }, { "id": "lilrb2-rs587709-bellenguez2022", "gene": "LILRB2", "variant": "rs587709", "chromosome": "19", "position_hg38": 54267597, "risk_allele": "C", "allele_frequency": 0.3251, "allele_frequency_source": "study-reported effect-allele frequency (GWAS Catalog GCST90027158)", "effect_size": "OR 1.05 (95% CI 1.04-1.07) per C allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 1.05, "ci_lower": 1.04, "ci_upper": 1.07, "p_value": 4e-11, "population": "39,106 European ancestry clinically diagnosed cases, 46,828 European ancestry proxy cases, 401,577 European ancestry controls (stage 1); replication 25,392 cases, 276,086 controls", "ancestry": "European", "study_name": "Bellenguez et al. 2022, Nat Genet (EADB/IGAP/UKB stage 1)", "n_cases": 85934, "n_controls": 401577, "year": 2022, "url": "https://www.ebi.ac.uk/gwas/studies/GCST90027158", "pubmed_id": "35379992", "classification": "low-risk/modifier", "category": "gwas-locus", "value_type": "measured", "notes": "New in Bellenguez 2022." }, { "id": "siglec11-rs9304690-bellenguez2022", "gene": "SIGLEC11", "variant": "rs9304690", "chromosome": "19", "position_hg38": 49950060, "risk_allele": "T", "allele_frequency": 0.2398, "allele_frequency_source": "study-reported effect-allele frequency (GWAS Catalog GCST90027158)", "effect_size": "OR 1.05 (95% CI 1.03-1.07) per T allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 1.05, "ci_lower": 1.03, "ci_upper": 1.07, "p_value": 5e-09, "population": "39,106 European ancestry clinically diagnosed cases, 46,828 European ancestry proxy cases, 401,577 European ancestry controls (stage 1); replication 25,392 cases, 276,086 controls", "ancestry": "European", "study_name": "Bellenguez et al. 2022, Nat Genet (EADB/IGAP/UKB stage 1)", "n_cases": 85934, "n_controls": 401577, "year": 2022, "url": "https://www.ebi.ac.uk/gwas/studies/GCST90027158", "pubmed_id": "35379992", "classification": "low-risk/modifier", "category": "gwas-locus", "value_type": "measured", "notes": "New in Bellenguez 2022." }, { "id": "abca7-rs115550680-reitz2013", "gene": "ABCA7", "variant": "rs115550680", "chromosome": "19", "position_hg38": 1050421, "risk_allele": "G", "allele_frequency": 0.07, "allele_frequency_source": "study-reported effect-allele frequency (GWAS Catalog GCST001963)", "effect_size": "OR 1.79 (95% CI 1.47-2.12) per G allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 1.79, "ci_lower": 1.47, "ci_upper": 2.12, "p_value": 2e-09, "population": "1,968 African American cases, 3,928 African American controls", "ancestry": "African", "study_name": "Reitz et al. 2013, JAMA (ADGC African American)", "n_cases": 1968, "n_controls": 3928, "year": 2013, "url": "https://www.ebi.ac.uk/gwas/studies/GCST001963", "pubmed_id": "23571587", "classification": "moderate-risk", "category": "multi-ancestry", "value_type": "measured", "notes": "Abstract: 'rs115550680, allele G; frequency 0.09 cases and 0.06 controls; OR 1.79 (95% CI 1.47-2.12); P 2.2e-9', an effect 'comparable with that of the APOE e4-determining SNP rs429358' in the same sample (OR 2.31, 2.19-2.42). gnomAD G allele: afr 0.057, nfe 0.0002 -- an African-ancestry-specific ABCA7 risk allele." }, { "id": "abca7-rs115550680-kunkle2021", "gene": "ABCA7", "variant": "rs115550680", "chromosome": "19", "position_hg38": 1050421, "risk_allele": null, "allele_frequency": null, "allele_frequency_source": null, "effect_size": "OR 1.58 (95% CI 1.32-1.88) (effect allele not specified in catalog record; OR may be inverted)", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 1.58, "ci_lower": 1.32, "ci_upper": 1.88, "p_value": 4e-07, "population": "2,784 African American cases, 5,222 African American controls", "ancestry": "African", "study_name": "Kunkle et al. 2021, JAMA Neurol (ADGC African American, African Genome Resources panel)", "n_cases": 2784, "n_controls": 5222, "year": 2021, "url": "https://www.ebi.ac.uk/gwas/studies/GCST011696", "pubmed_id": "33074286", "classification": "moderate-risk", "category": "multi-ancestry", "value_type": "measured", "notes": "Same African-American ABCA7 variant in the expanded 2021 ADGC analysis (OR 1.58, 1.32-1.88; P 4e-7)." }, { "id": "apoc1-rs157591-kunkle2021", "gene": "APOC1 / APOE region", "variant": "rs157591", "chromosome": "19", "position_hg38": 44920677, "risk_allele": null, "allele_frequency": null, "allele_frequency_source": null, "effect_size": "OR 1.93 (95% CI 1.72-2.17) (effect allele not specified in catalog record; OR may be inverted)", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 1.93, "ci_lower": 1.72, "ci_upper": 2.17, "p_value": 2e-25, "population": "2,784 African American cases, 5,222 African American controls", "ancestry": "African", "study_name": "Kunkle et al. 2021, JAMA Neurol (ADGC African American, African Genome Resources panel)", "n_cases": 2784, "n_controls": 5222, "year": 2021, "url": "https://www.ebi.ac.uk/gwas/studies/GCST011696", "pubmed_id": "33074286", "classification": "high-risk", "category": "multi-ancestry", "value_type": "measured", "notes": "APOE-region lead in African Americans (OR 1.93, 1.72-2.17)." }, { "id": "intergenic-rs570487962-kunkle2021", "gene": "intergenic 15q26 near IGF1R (catalog maps LINC00923/LINC02253)", "variant": "rs570487962", "chromosome": "15", "position_hg38": 97449455, "risk_allele": null, "allele_frequency": null, "allele_frequency_source": null, "effect_size": "OR 0.10 (95% CI 0.05-0.22) (effect allele not specified in catalog record; OR may be inverted)", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 0.1, "ci_lower": 0.05, "ci_upper": 0.22, "p_value": 2e-09, "population": "2,784 African American cases, 5,222 African American controls", "ancestry": "African", "study_name": "Kunkle et al. 2021, JAMA Neurol (ADGC African American, African Genome Resources panel)", "n_cases": 2784, "n_controls": 5222, "year": 2021, "url": "https://www.ebi.ac.uk/gwas/studies/GCST011696", "pubmed_id": "33074286", "classification": "protective", "category": "multi-ancestry", "value_type": "measured", "notes": "Abstract: 'genome-wide significant intergenic locus near IGF1R at 15q26 (P = 1.7e-9)'; rare variant, catalog OR 0.10 (0.05-0.22). Rare-variant ORs of this size in ~8,000 samples are unstable; not replicated in Europeans (variant absent)." }, { "id": "alcam-rs2633682-kunkle2021", "gene": "ALCAM", "variant": "rs2633682", "chromosome": "3", "position_hg38": 104690364, "risk_allele": null, "allele_frequency": null, "allele_frequency_source": null, "effect_size": "OR 0.78 (95% CI 0.71-0.86) (effect allele not specified in catalog record; OR may be inverted)", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 0.78, "ci_lower": 0.71, "ci_upper": 0.86, "p_value": 9e-07, "population": "2,784 African American cases, 5,222 African American controls", "ancestry": "African", "study_name": "Kunkle et al. 2021, JAMA Neurol (ADGC African American, African Genome Resources panel)", "n_cases": 2784, "n_controls": 5222, "year": 2021, "url": "https://www.ebi.ac.uk/gwas/studies/GCST011696", "pubmed_id": "33074286", "classification": "disputed", "category": "multi-ancestry", "value_type": "measured", "notes": "Suggestive (P 9.3e-7) novel common locus in African Americans; ALCAM expression associated with brain amyloid load. Not genome-wide significant; listed because these are the candidate African-American-specific loci highlighted by the authors." }, { "id": "gpc6-rs9516245-kunkle2021", "gene": "GPC6", "variant": "rs9516245", "chromosome": "13", "position_hg38": 93507547, "risk_allele": null, "allele_frequency": null, "allele_frequency_source": null, "effect_size": "OR 1.73 (95% CI 1.39-2.15) (effect allele not specified in catalog record; OR may be inverted)", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 1.73, "ci_lower": 1.39, "ci_upper": 2.15, "p_value": 4e-07, "population": "2,784 African American cases, 5,222 African American controls", "ancestry": "African", "study_name": "Kunkle et al. 2021, JAMA Neurol (ADGC African American, African Genome Resources panel)", "n_cases": 2784, "n_controls": 5222, "year": 2021, "url": "https://www.ebi.ac.uk/gwas/studies/GCST011696", "pubmed_id": "33074286", "classification": "disputed", "category": "multi-ancestry", "value_type": "measured", "notes": "Suggestive (P 4.1e-7). Not genome-wide significant; listed because these are the candidate African-American-specific loci highlighted by the authors." }, { "id": "vrk3-rs3745495-kunkle2021", "gene": "VRK3", "variant": "rs3745495", "chromosome": "19", "position_hg38": 50021075, "risk_allele": null, "allele_frequency": null, "allele_frequency_source": null, "effect_size": "OR 1.39 (95% CI 1.23-1.56) (effect allele not specified in catalog record; OR may be inverted)", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 1.39, "ci_lower": 1.23, "ci_upper": 1.56, "p_value": 4e-07, "population": "2,784 African American cases, 5,222 African American controls", "ancestry": "African", "study_name": "Kunkle et al. 2021, JAMA Neurol (ADGC African American, African Genome Resources panel)", "n_cases": 2784, "n_controls": 5222, "year": 2021, "url": "https://www.ebi.ac.uk/gwas/studies/GCST011696", "pubmed_id": "33074286", "classification": "disputed", "category": "multi-ancestry", "value_type": "measured", "notes": "Suggestive (P 3.5e-7). Not genome-wide significant; listed because these are the candidate African-American-specific loci highlighted by the authors." }, { "id": "kunkle2021-transferability-of-nhw-loci-to-african-americans", "gene": "25 known European (NHW) loci", "variant": "locus-level replication", "chromosome": null, "position_hg38": null, "risk_allele": null, "allele_frequency": null, "allele_frequency_source": null, "effect_size": "Of 25 known NHW AD loci, only 7 (APOE, ABCA7, TREM2, BIN1, CD2AP, FERMT2, WWOX) reached nominal significance or stronger in African Americans", "effect_size_type": "count of replicated loci", "odds_ratio": null, "ci_lower": null, "ci_upper": null, "p_value": null, "population": "2,784 African American cases, 5,222 African American controls", "ancestry": "African", "study_name": "Kunkle et al. 2021, JAMA Neurol (ADGC African American, African Genome Resources panel)", "n_cases": 2784, "n_controls": 5222, "year": 2021, "url": "https://doi.org/10.1001/jamaneurol.2020.3536", "pubmed_id": "33074286", "classification": "caveat", "category": "caveat", "value_type": "measured", "notes": "Abstract also: 'African American individuals from the same community are approximately twice as likely to develop Alzheimer disease' yet 'the largest ... GWAS to date have been conducted in non-Hispanic White individuals'. Pathways overlap; the specific loci differ." }, { "id": "abca7-rs73505251-sherva2023", "gene": "ABCA7 (African-ancestry lead; catalog maps ARHGAP45)", "variant": "rs73505251", "chromosome": "19", "position_hg38": 1068096, "risk_allele": "A", "allele_frequency": null, "allele_frequency_source": null, "effect_size": "p = 3e-10 (effect size not curated)", "effect_size_type": "p-value only", "odds_ratio": null, "ci_lower": null, "ci_upper": null, "p_value": 3e-10, "population": "6,796 African American cases, 4,385 African American maternal proxy cases, 2,256 African American paternal proxy cases, 69,627 African American controls", "ancestry": "African", "study_name": "Sherva et al. 2023, Mol Psychiatry (Million Veteran Program African ancestry ADRD + proxy, meta-analysed with ADGC)", "n_cases": 6796, "n_controls": 69627, "year": 2023, "url": "https://www.ebi.ac.uk/gwas/studies/GCST90267627", "pubmed_id": "36543923", "classification": "low-risk/modifier", "category": "multi-ancestry", "value_type": "measured", "notes": "P 3.26e-10; peak differs from European and prior AA leads. Phenotype is ADRD (incl. vascular/non-specific dementia) plus parental-proxy dementia in a predominantly male Veteran cohort; ORs were not curated by the catalog." }, { "id": "cd2ap-rs7738720-sherva2023", "gene": "CD2AP (African-ancestry lead)", "variant": "rs7738720", "chromosome": "6", "position_hg38": 47427663, "risk_allele": "T", "allele_frequency": null, "allele_frequency_source": null, "effect_size": "p = 1e-09 (effect size not curated)", "effect_size_type": "p-value only", "odds_ratio": null, "ci_lower": null, "ci_upper": null, "p_value": 1e-09, "population": "6,796 African American cases, 4,385 African American maternal proxy cases, 2,256 African American paternal proxy cases, 69,627 African American controls", "ancestry": "African", "study_name": "Sherva et al. 2023, Mol Psychiatry (Million Veteran Program African ancestry ADRD + proxy, meta-analysed with ADGC)", "n_cases": 6796, "n_controls": 69627, "year": 2023, "url": "https://www.ebi.ac.uk/gwas/studies/GCST90267627", "pubmed_id": "36543923", "classification": "low-risk/modifier", "category": "multi-ancestry", "value_type": "measured", "notes": "P 1.14e-9. Phenotype is ADRD (incl. vascular/non-specific dementia) plus parental-proxy dementia in a predominantly male Veteran cohort; ORs were not curated by the catalog." }, { "id": "robo1-rs11919682-sherva2023", "gene": "ROBO1", "variant": "rs11919682", "chromosome": "3", "position_hg38": 78720952, "risk_allele": "C", "allele_frequency": null, "allele_frequency_source": null, "effect_size": "p = 2e-08 (effect size not curated)", "effect_size_type": "p-value only", "odds_ratio": null, "ci_lower": null, "ci_upper": null, "p_value": 2e-08, "population": "6,796 African American cases, 4,385 African American maternal proxy cases, 2,256 African American paternal proxy cases, 69,627 African American controls", "ancestry": "African", "study_name": "Sherva et al. 2023, Mol Psychiatry (Million Veteran Program African ancestry ADRD + proxy, meta-analysed with ADGC)", "n_cases": 6796, "n_controls": 69627, "year": 2023, "url": "https://www.ebi.ac.uk/gwas/studies/GCST90267627", "pubmed_id": "36543923", "classification": "low-risk/modifier", "category": "multi-ancestry", "value_type": "measured", "notes": "Novel in African ancestry (P 1.63e-8), common-variant meta-analysis of MVP ADRD + proxy. Phenotype is ADRD (incl. vascular/non-specific dementia) plus parental-proxy dementia in a predominantly male Veteran cohort; ORs were not curated by the catalog." }, { "id": "mpdz-rs141610415-ray2024-african", "gene": "MPDZ", "variant": "rs141610415", "chromosome": "9", "position_hg38": 13220519, "risk_allele": null, "allele_frequency": 0.002, "allele_frequency_source": "study-reported MAF (abstract)", "effect_size": "P 3.68e-9, MAF 0.002 (novel African-ancestry locus); catalog beta 3.5 (95% CI 2.17-4.83), P 2e-7 for the within-dataset meta-analysis record", "effect_size_type": "p-value; beta as curated (scale not stated)", "odds_ratio": null, "ci_lower": null, "ci_upper": null, "p_value": 3.68e-09, "population": "77 African ancestry cases, 628 African ancestry controls, 2,826 African American cases, 5,637 African American controls", "ancestry": "African", "study_name": "Ray et al. 2024, Alzheimers Dement (ADGC African ancestry, African Genome Resources panel)", "n_cases": 2903, "n_controls": 6265, "year": 2024, "url": "https://doi.org/10.1002/alz.13880", "pubmed_id": "38958117", "classification": "disputed", "category": "multi-ancestry", "value_type": "measured", "notes": "Very rare variant; gnomAD C allele afr 0.0024, nfe 0. Authors: association patterns at chr12q23.2 (ASCL1) differed by degree of African ancestry, i.e. local ancestry modulates some associations. Classified 'disputed' pending replication." }, { "id": "fam47e/scarb2-rs920608-shigemizu2021", "gene": "FAM47E/SCARB2 region", "variant": "rs920608", "chromosome": "4", "position_hg38": 76217307, "risk_allele": "C", "allele_frequency": 0.046, "allele_frequency_source": "study-reported effect-allele frequency (GWAS Catalog GCST012215)", "effect_size": "OR 0.65 (95% CI 0.57-0.75) per C allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 0.65, "ci_lower": 0.57, "ci_upper": 0.75, "p_value": 5e-09, "population": "3,962 Japanese ancestry cases, 4,074 Japanese ancestry controls; replication 1,216 cases, 2,446 controls", "ancestry": "East-Asian", "study_name": "Shigemizu et al. 2021, Transl Psychiatry (Japanese GWAS)", "n_cases": 3962, "n_controls": 4074, "year": 2021, "url": "https://www.ebi.ac.uk/gwas/studies/GCST012215", "pubmed_id": "33654092", "classification": "protective", "category": "multi-ancestry", "value_type": "measured", "notes": "Novel Japanese locus (OR 0.65, 0.57-0.75, P 5e-9 in meta-analysis with replication). gnomAD C allele: eas 0.043, nfe 0.009, afr 0.089." }, { "id": "or2b2-rs1497525-shigemizu2021", "gene": "OR2B2", "variant": "rs1497525", "chromosome": "6", "position_hg38": 27915491, "risk_allele": null, "allele_frequency": null, "allele_frequency_source": null, "effect_size": "p = 2e-08 (effect size not curated)", "effect_size_type": "p-value only", "odds_ratio": null, "ci_lower": null, "ci_upper": null, "p_value": 2e-08, "population": "3,962 Japanese ancestry cases, 4,074 Japanese ancestry controls, 21,982 European ancestry cases, 41,944 European ancestry controls", "ancestry": "multi", "study_name": "Shigemizu et al. 2021, Transl Psychiatry (Japanese + IGAP trans-ethnic meta-analysis)", "n_cases": 25944, "n_controls": 46018, "year": 2021, "url": "https://www.ebi.ac.uk/gwas/studies/GCST012214", "pubmed_id": "33654092", "classification": "low-risk/modifier", "category": "multi-ancestry", "value_type": "measured", "notes": "Novel locus from Japanese + IGAP trans-ethnic meta-analysis (P 2e-8); effect size not curated." }, { "id": "sorl1-rs11218343-miyashita2013-japanese-korean", "gene": "SORL1", "variant": "rs11218343", "chromosome": "11", "position_hg38": 121564878, "risk_allele": "C (protective)", "allele_frequency": 0.2994, "allele_frequency_source": "gnomAD genomes East Asian via Ensembl release 116 (C allele; nfe 0.039)", "effect_size": "P 1.77e-9 (combined Japanese + Korean + Caucasian); OR not in abstract", "effect_size_type": "p-value only", "odds_ratio": null, "ci_lower": null, "ci_upper": null, "p_value": 1.77e-09, "population": "Japanese stage 1: 1,008 cases / 1,016 controls; stage 2: 885 / 985; Korean 339 / 1,129; Caucasian ADGC 11,840 / 10,931", "ancestry": "multi", "study_name": "Miyashita et al. 2013, PLoS One (JGSCAD/ADGC)", "n_cases": 14072, "n_controls": 14061, "year": 2013, "url": "https://doi.org/10.1371/journal.pone.0058618", "pubmed_id": "23565137", "classification": "protective", "category": "multi-ancestry", "value_type": "measured", "notes": "First genome-wide-significant SORL1 association, made possible by the much higher East Asian allele frequency. PICALM rs3851179 (P 1.7e-5) and BIN1 rs744373 (P 1.4e-4) replicated in Japanese with the same risk alleles as Caucasians. n_cases/n_controls sum all stages." }, { "id": "rhobtb3-rs3777215-jia2021-chinese", "gene": "RHOBTB3/GLRX (intron)", "variant": "rs3777215", "chromosome": "5", "position_hg38": 95786296, "risk_allele": null, "allele_frequency": null, "allele_frequency_source": null, "effect_size": "OR 0.69, P 3.07e-19", "effect_size_type": "odds ratio (allele not stated in text loaded)", "odds_ratio": 0.69, "ci_lower": null, "ci_upper": null, "p_value": 3.07e-19, "population": "Two-stage Chinese GWAS: 3,913 AD cases and 7,593 controls; validated in a longitudinal cohort of 5,474", "ancestry": "East-Asian", "study_name": "Jia et al. 2021, Brain (Chinese GWAS)", "n_cases": 3913, "n_controls": 7593, "year": 2021, "url": "https://doi.org/10.1093/brain/awaa364", "pubmed_id": "33188687", "classification": "protective", "category": "multi-ancestry", "value_type": "measured", "notes": "ORs read from the PMC full text (PMC8041344); CIs and effect alleles were in supplementary tables not loaded. Not in the GWAS Catalog. Position from Ensembl release 116." }, { "id": "intergenic-rs6859823-jia2021-chinese", "gene": "intergenic chr5 (RNA5SP189-CTC-278L1.1)", "variant": "rs6859823", "chromosome": "5", "position_hg38": 106218683, "risk_allele": null, "allele_frequency": null, "allele_frequency_source": null, "effect_size": "OR 0.74, P 2.49e-23; also genome-wide significant in IGAP stage 1", "effect_size_type": "odds ratio (allele not stated in text loaded)", "odds_ratio": 0.74, "ci_lower": null, "ci_upper": null, "p_value": 2.49e-23, "population": "Two-stage Chinese GWAS: 3,913 AD cases and 7,593 controls; validated in a longitudinal cohort of 5,474", "ancestry": "East-Asian", "study_name": "Jia et al. 2021, Brain (Chinese GWAS)", "n_cases": 3913, "n_controls": 7593, "year": 2021, "url": "https://doi.org/10.1093/brain/awaa364", "pubmed_id": "33188687", "classification": "protective", "category": "multi-ancestry", "value_type": "measured", "notes": "ORs read from the PMC full text (PMC8041344); CIs and effect alleles were in supplementary tables not loaded. Not in the GWAS Catalog. Position from Ensembl release 116." }, { "id": "chr14-rs234434-jia2021-chinese", "gene": "chr14 (novel Chinese locus)", "variant": "rs234434", "chromosome": "14", "position_hg38": 97354683, "risk_allele": null, "allele_frequency": null, "allele_frequency_source": null, "effect_size": "OR 1.71, P 1.35e-67", "effect_size_type": "odds ratio (allele not stated in text loaded)", "odds_ratio": 1.71, "ci_lower": null, "ci_upper": null, "p_value": 1.35e-67, "population": "Two-stage Chinese GWAS: 3,913 AD cases and 7,593 controls; validated in a longitudinal cohort of 5,474", "ancestry": "East-Asian", "study_name": "Jia et al. 2021, Brain (Chinese GWAS)", "n_cases": 3913, "n_controls": 7593, "year": 2021, "url": "https://doi.org/10.1093/brain/awaa364", "pubmed_id": "33188687", "classification": "moderate-risk", "category": "multi-ancestry", "value_type": "measured", "notes": "ORs read from the PMC full text (PMC8041344); CIs and effect alleles were in supplementary tables not loaded. Not in the GWAS Catalog. Position from Ensembl release 116." }, { "id": "chodl-rs2255835-jia2021-chinese", "gene": "CHODL (intron)", "variant": "rs2255835", "chromosome": "21", "position_hg38": 18119346, "risk_allele": null, "allele_frequency": null, "allele_frequency_source": null, "effect_size": "OR 1.23, P 4.81e-9", "effect_size_type": "odds ratio (allele not stated in text loaded)", "odds_ratio": 1.23, "ci_lower": null, "ci_upper": null, "p_value": 4.81e-09, "population": "Two-stage Chinese GWAS: 3,913 AD cases and 7,593 controls; validated in a longitudinal cohort of 5,474", "ancestry": "East-Asian", "study_name": "Jia et al. 2021, Brain (Chinese GWAS)", "n_cases": 3913, "n_controls": 7593, "year": 2021, "url": "https://doi.org/10.1093/brain/awaa364", "pubmed_id": "33188687", "classification": "moderate-risk", "category": "multi-ancestry", "value_type": "measured", "notes": "ORs read from the PMC full text (PMC8041344); CIs and effect alleles were in supplementary tables not loaded. Not in the GWAS Catalog. Position from Ensembl release 116." }, { "id": "apoe-rs429358-rajabli2025", "gene": "APOE", "variant": "rs429358", "chromosome": "19", "position_hg38": 44908684, "risk_allele": "T", "allele_frequency": null, "allele_frequency_source": null, "effect_size": "OR 3.10 (95% CI 2.75-3.49) per T allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 3.1, "ci_lower": 2.75, "ci_upper": 3.49, "p_value": 1e-320, "population": "17,839 European ancestry cases, 19,543 European ancestry controls, 2,114 African American cases, 4,614 African American controls, 3,112 Hispanic cases, 5,787 Hispanic controls, 1,430 East Asian ancestry cases, 1,802 East Asian ancestry controls", "ancestry": "multi", "study_name": "Rajabli et al. 2025, Genome Biol (ADGC cross-ancestry random-effects meta-analysis)", "n_cases": 24495, "n_controls": 31746, "year": 2025, "url": "https://www.ebi.ac.uk/gwas/studies/GCST90654655", "pubmed_id": "40676597", "classification": "high-risk", "category": "multi-ancestry", "value_type": "measured", "notes": "Cross-ancestry random-effects estimate for the e4-defining SNP: OR 3.10 (2.75-3.49) per allele. Ancestry-specific: African American stratum chr19:44908684-T OR 0.376 (0.34-0.39) for the non-e4 T allele (frequency 0.759); Hispanic stratum OR 0.443 (0.41-0.46) for T (freq 0.797)." }, { "id": "apoe-rs7412-rajabli2025", "gene": "APOE", "variant": "rs7412", "chromosome": "19", "position_hg38": 44908822, "risk_allele": "T", "allele_frequency": null, "allele_frequency_source": null, "effect_size": "OR 0.54 (95% CI 0.50-0.60) per T allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 0.54, "ci_lower": 0.5, "ci_upper": 0.6, "p_value": 4e-106, "population": "17,839 European ancestry cases, 19,543 European ancestry controls, 2,114 African American cases, 4,614 African American controls, 3,112 Hispanic cases, 5,787 Hispanic controls, 1,430 East Asian ancestry cases, 1,802 East Asian ancestry controls", "ancestry": "multi", "study_name": "Rajabli et al. 2025, Genome Biol (ADGC cross-ancestry random-effects meta-analysis)", "n_cases": 24495, "n_controls": 31746, "year": 2025, "url": "https://www.ebi.ac.uk/gwas/studies/GCST90654655", "pubmed_id": "40676597", "classification": "protective", "category": "multi-ancestry", "value_type": "measured", "notes": "Cross-ancestry estimate for the e2-defining SNP: OR 0.54 (0.50-0.60) per T allele." }, { "id": "lrrc4c-rs12576934-rajabli2025", "gene": "LRRC4C (author-reported; catalog maps LINC01499)", "variant": "rs12576934", "chromosome": "11", "position_hg38": 41714561, "risk_allele": "A", "allele_frequency": null, "allele_frequency_source": null, "effect_size": "OR 1.12 (95% CI 1.08-1.16) per A allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 1.12, "ci_lower": 1.08, "ci_upper": 1.16, "p_value": 5e-09, "population": "17,839 European ancestry cases, 19,543 European ancestry controls, 2,114 African American cases, 4,614 African American controls, 3,112 Hispanic cases, 5,787 Hispanic controls, 1,430 East Asian ancestry cases, 1,802 East Asian ancestry controls", "ancestry": "multi", "study_name": "Rajabli et al. 2025, Genome Biol (ADGC cross-ancestry random-effects meta-analysis)", "n_cases": 24495, "n_controls": 31746, "year": 2025, "url": "https://www.ebi.ac.uk/gwas/studies/GCST90654655", "pubmed_id": "40676597", "classification": "low-risk/modifier", "category": "multi-ancestry", "value_type": "measured", "notes": "Novel cross-population locus 11p12 (abstract: LRRC4C). OR 1.12 (1.08-1.16), P 5e-9. gnomAD A allele frequency: nfe 0.164, eas 0.419, afr 0 (not observed) -- detection depended on non-African populations." }, { "id": "lhx5-as1-rs111486601-rajabli2025", "gene": "LHX5-AS1 (author-reported; catalog maps LINC01234)", "variant": "rs111486601", "chromosome": "12", "position_hg38": 113643122, "risk_allele": "T", "allele_frequency": null, "allele_frequency_source": null, "effect_size": "OR 0.63 (95% CI 0.32-0.81) per T allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 0.63, "ci_lower": 0.32, "ci_upper": 0.81, "p_value": 1e-08, "population": "17,839 European ancestry cases, 19,543 European ancestry controls, 2,114 African American cases, 4,614 African American controls, 3,112 Hispanic cases, 5,787 Hispanic controls, 1,430 East Asian ancestry cases, 1,802 East Asian ancestry controls", "ancestry": "multi", "study_name": "Rajabli et al. 2025, Genome Biol (ADGC cross-ancestry random-effects meta-analysis)", "n_cases": 24495, "n_controls": 31746, "year": 2025, "url": "https://www.ebi.ac.uk/gwas/studies/GCST90654655", "pubmed_id": "40676597", "classification": "protective", "category": "multi-ancestry", "value_type": "measured", "notes": "Novel cross-population locus 12q24.13 (abstract: LHX5-AS1); OR 0.63 (0.32-0.81), P 1e-8. Driven by the Hispanic stratum where chr12:113643122-T has OR 0.44 (0.34-0.50), P 5e-10, frequency 0.039; gnomAD T allele nfe 0.0002, amr 0.0022, eas 0." }, { "id": "locus-chr2-164244154-rajabli2025-hispanic", "gene": null, "variant": "2:164244154", "chromosome": "2", "position_hg38": 164244154, "risk_allele": "A", "allele_frequency": 0.0383, "allele_frequency_source": "study-reported effect-allele frequency (GWAS Catalog GCST90654649)", "effect_size": "OR 0.47 (95% CI 0.36-0.54) per A allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 0.4719888, "ci_lower": 0.36, "ci_upper": 0.54, "p_value": 2e-08, "population": "3,112 Hispanic cases, 5,787 Hispanic controls", "ancestry": "Hispanic", "study_name": "Rajabli et al. 2025, Genome Biol (ADGC Hispanic stratum)", "n_cases": 3112, "n_controls": 5787, "year": 2025, "url": "https://www.ebi.ac.uk/gwas/studies/GCST90654649", "pubmed_id": "40676597", "classification": "protective", "category": "multi-ancestry", "value_type": "measured", "notes": "Hispanic-specific genome-wide-significant locus (OR 0.47, 0.36-0.54, P 2e-8, frequency 0.038). The abstract names GRB14 and PTPRK as Hispanic-specific loci; the catalog record gives coordinates only, so no gene is asserted here." }, { "id": "locus-chr9-109849671-rajabli2025-eastasian", "gene": null, "variant": "9:109849671", "chromosome": "9", "position_hg38": 109849671, "risk_allele": "A", "allele_frequency": 0.731, "allele_frequency_source": "study-reported effect-allele frequency (GWAS Catalog GCST90654650)", "effect_size": "OR 0.63 (95% CI 0.54-0.69) per A allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 0.6345114, "ci_lower": 0.54, "ci_upper": 0.69, "p_value": 2e-08, "population": "1,430 East Asian ancestry cases, 1,802 East Asian ancestry controls", "ancestry": "East-Asian", "study_name": "Rajabli et al. 2025, Genome Biol (ADGC East Asian stratum)", "n_cases": 1430, "n_controls": 1802, "year": 2025, "url": "https://www.ebi.ac.uk/gwas/studies/GCST90654650", "pubmed_id": "40676597", "classification": "protective", "category": "multi-ancestry", "value_type": "measured", "notes": "East Asian stratum genome-wide-significant locus (OR 0.63, 0.54-0.69, P 2e-8) in only 1,430 cases / 1,802 controls; gene not curated; treat as provisional." }, { "id": "sharpin-rs34173062-rajabli2025", "gene": "SHARPIN", "variant": "rs34173062", "chromosome": "8", "position_hg38": 144103704, "risk_allele": "A", "allele_frequency": null, "allele_frequency_source": null, "effect_size": "OR 1.20 (95% CI 1.04-1.39) per A allele", "effect_size_type": "odds ratio per effect allele", "odds_ratio": 1.2, "ci_lower": 1.04, "ci_upper": 1.39, "p_value": 2e-09, "population": "17,839 European ancestry cases, 19,543 European ancestry controls, 2,114 African American cases, 4,614 African American controls, 3,112 Hispanic cases, 5,787 Hispanic controls, 1,430 East Asian ancestry cases, 1,802 East Asian ancestry controls", "ancestry": "multi", "study_name": "Rajabli et al. 2025, Genome Biol (ADGC cross-ancestry random-effects meta-analysis)", "n_cases": 24495, "n_controls": 31746, "year": 2025, "url": "https://www.ebi.ac.uk/gwas/studies/GCST90654655", "pubmed_id": "40676597", "classification": "low-risk/modifier", "category": "multi-ancestry", "value_type": "measured", "notes": "Abstract: 'we detect the SHARPIN locus with only 13.7% of the sample size of the NHW GWAS study (n = 409,589) in which this locus was first observed' -- illustrates the power of diverse-ancestry haplotypes." }, { "id": "trank1-rs9867455-lake2023", "gene": "TRANK1", "variant": "rs9867455", "chromosome": "3", "position_hg38": 36911933, "risk_allele": "A", "allele_frequency": 0.405, "allele_frequency_source": "study-reported effect-allele frequency (GWAS Catalog GCST90301303)", "effect_size": "p = 7e-08 (effect size not curated)", "effect_size_type": "p-value only", "odds_ratio": null, "ci_lower": null, "ci_upper": null, "p_value": 7e-08, "population": "93,263 European ancestry cases, 532,679 European ancestry controls, 2,748 African ancestry cases, 5,222 African ancestry controls, 3,962 East Asian ancestry cases, 4,074 East Asian ancestry controls, 1,088 Hispanic or Latin American cases, 1,152 Hispanic or Latin American controls", "ancestry": "multi", "study_name": "Lake et al. 2023, Mol Psychiatry (multi-ancestry meta-analysis)", "n_cases": 101061, "n_controls": 543127, "year": 2023, "url": "https://www.ebi.ac.uk/gwas/studies/GCST90301303", "pubmed_id": "37198259", "classification": "disputed", "category": "multi-ancestry", "value_type": "measured", "notes": "Chromosome 3 locus in the Lake 2023 multi-ancestry meta-analysis; abstract reports 'two independent novel disease-associated loci on chromosome 3'. In the catalog record this variant is P 7e-8 / 2e-7 (just above 5e-8), and effect sizes were not curated -- provisional." }, { "id": "abcf3/vwa5b2-rs9837978-lake2023", "gene": "ABCF3/VWA5B2", "variant": "rs9837978", "chromosome": "3", "position_hg38": 184219159, "risk_allele": "G", "allele_frequency": 0.287, "allele_frequency_source": "study-reported effect-allele frequency (GWAS Catalog GCST90301303)", "effect_size": "p = 2e-07 (effect size not curated)", "effect_size_type": "p-value only", "odds_ratio": null, "ci_lower": null, "ci_upper": null, "p_value": 2e-07, "population": "93,263 European ancestry cases, 532,679 European ancestry controls, 2,748 African ancestry cases, 5,222 African ancestry controls, 3,962 East Asian ancestry cases, 4,074 East Asian ancestry controls, 1,088 Hispanic or Latin American cases, 1,152 Hispanic or Latin American controls", "ancestry": "multi", "study_name": "Lake et al. 2023, Mol Psychiatry (multi-ancestry meta-analysis)", "n_cases": 101061, "n_controls": 543127, "year": 2023, "url": "https://www.ebi.ac.uk/gwas/studies/GCST90301303", "pubmed_id": "37198259", "classification": "disputed", "category": "multi-ancestry", "value_type": "measured", "notes": "Chromosome 3 locus in the Lake 2023 multi-ancestry meta-analysis; abstract reports 'two independent novel disease-associated loci on chromosome 3'. In the catalog record this variant is P 7e-8 / 2e-7 (just above 5e-8), and effect sizes were not curated -- provisional." }, { "id": "prs-escottprice2015-auc", "gene": "polygenic", "variant": "PRS (IGAP weights) + APOE + age + sex", "chromosome": null, "position_hg38": null, "risk_allele": null, "allele_frequency": null, "allele_frequency_source": null, "effect_size": "AUC 0.782 (95% CI 0.77-0.80) with APOE, PRS, sex and age as predictors", "effect_size_type": "AUC", "odds_ratio": null, "ci_lower": null, "ci_upper": null, "p_value": null, "population": "Training: IGAP 17,008 cases / 37,154 controls; prediction subset 3,049 cases / 1,554 controls with APOE genotypes; European ancestry", "ancestry": "European", "study_name": "Escott-Price et al. 2015, Brain", "n_cases": 3049, "n_controls": 1554, "year": 2015, "url": "https://doi.org/10.1093/brain/awv268", "pubmed_id": "26490334", "classification": "caveat", "category": "prs", "value_type": "measured", "notes": "Polygenic component significant even after excluding APOE and known loci (P 3.4e-19). This 0.78 figure is the most-cited PRS benchmark; note it includes age and sex." }, { "id": "prs-escottprice2017-pathology-confirmed-auc", "gene": "polygenic", "variant": "PRS + APOE, pathologically confirmed cases/controls", "chromosome": null, "position_hg38": null, "risk_allele": null, "allele_frequency": null, "allele_frequency_source": null, "effect_size": "AUC 0.84 in a pathological case-control series (vs <0.80 in clinical series)", "effect_size_type": "AUC", "odds_ratio": null, "ci_lower": null, "ci_upper": null, "p_value": null, "population": "Pathologically confirmed AD cases and controls (n not in abstract); European ancestry", "ancestry": "European", "study_name": "Escott-Price et al. 2017, Ann Neurol", "n_cases": null, "n_controls": null, "year": 2017, "url": "https://doi.org/10.1002/ana.24999", "pubmed_id": "28727176", "classification": "caveat", "category": "prs", "value_type": "measured", "notes": "Authors 'suggest ... there is limited room for further improvement using genetic data'. Higher AUC reflects cleaner phenotypes, not a better score." }, { "id": "prs-leonenko2021-auc-and-extremes", "gene": "polygenic", "variant": "APOE (e2+e4) + PRS excluding APOE region, pT<=0.1", "chromosome": null, "position_hg38": null, "risk_allele": null, "allele_frequency": null, "allele_frequency_source": null, "effect_size": "AUC 74.1% (best model); APOE alone AUC 70.0%; PRS without APOE 61.3%; individuals at +/-2 SD extremes OR 124 (95% CI 6-2707)", "effect_size_type": "AUC; OR at distribution extremes", "odds_ratio": null, "ci_lower": null, "ci_upper": null, "p_value": null, "population": "IGAP-derived weights applied to a European-ancestry case-control sample (n in Table 2 of paper; not in abstract)", "ancestry": "European", "study_name": "Leonenko et al. 2021, Nat Commun", "n_cases": null, "n_controls": null, "year": 2021, "url": "https://doi.org/10.1038/s41467-021-24082-z", "pubmed_id": "34301930", "classification": "caveat", "category": "prs", "value_type": "measured", "notes": "Read from PMC8302739. Key limits: prediction accuracy is similar across PRS methods but individual rankings differ; scores must be standardised against a population (not sample) mean to be comparable. The extreme-tail OR has an enormous CI." }, { "id": "prs-bellenguez2022-decile-risk", "gene": "polygenic", "variant": "Bellenguez 2022 genetic risk score (excl. APOE)", "chromosome": null, "position_hg38": null, "risk_allele": null, "allele_frequency": null, "allele_frequency_source": null, "effect_size": "1.6- to 1.9-fold increase in AD risk from lowest to highest decile, in addition to age and APOE e4 effects", "effect_size_type": "risk ratio, top vs bottom decile", "odds_ratio": null, "ci_lower": null, "ci_upper": null, "p_value": null, "population": "Independent European cohorts (Rotterdam, Three-City etc.; abstract) -- validation of a score built from 111,326 cases / 677,663 controls", "ancestry": "European", "study_name": "Bellenguez et al. 2022, Nat Genet", "n_cases": null, "n_controls": null, "year": 2022, "url": "https://doi.org/10.1038/s41588-022-01024-z", "pubmed_id": "35379992", "classification": "caveat", "category": "prs", "value_type": "measured", "notes": "Also predicted progression from MCI to AD/dementia. Modest gradient: the non-APOE polygenic component moves risk <2-fold across the whole distribution." }, { "id": "prs-bellou2025-benchmark-auc", "gene": "polygenic", "variant": "APOE + remaining PRS (best of 5 modelling approaches x 3 PRS methods x 2 GWAS)", "chromosome": null, "position_hg38": null, "risk_allele": null, "allele_frequency": null, "allele_frequency_source": null, "effect_size": "AUC 0.72-0.76; microglia-region-only PRS AUC 0.71-0.74; individual risk scores differed by up to 70% depending on which GWAS summary statistics were used", "effect_size_type": "AUC range", "odds_ratio": null, "ci_lower": null, "ci_upper": null, "p_value": null, "population": "ADNI (N = 568) and BioFINDER (N = 766); European-ancestry research cohorts", "ancestry": "European", "study_name": "Bellou et al. 2025, Alzheimers Res Ther", "n_cases": null, "n_controls": null, "year": 2025, "url": "https://doi.org/10.1186/s13195-024-01664-9", "pubmed_id": "39762974", "classification": "caveat", "category": "prs", "value_type": "measured", "notes": "Most recent benchmark; shows PRS instability at the individual level even within European ancestry." }, { "id": "prs-jung2022-korean-transferability", "gene": "polygenic", "variant": "European (IGAP)-derived PRS applied to Koreans", "chromosome": null, "position_hg38": null, "risk_allele": null, "allele_frequency": null, "allele_frequency_source": null, "effect_size": "OR 1.95 (95% CI 1.40-2.72) for AD dementia per PRS unit, independent of APOE e4 (dataset 1); OR 1.85 (1.05-3.32) in dataset 2; amyloid PET positivity OR 1.81 (1.32-2.48)", "effect_size_type": "odds ratio (PRS scale not stated in text loaded)", "odds_ratio": 1.95, "ci_lower": 1.4, "ci_upper": 2.72, "p_value": null, "population": "1,634 Koreans: 716 AD dementia, 222 aMCI, 699 cognitively unimpaired", "ancestry": "East-Asian", "study_name": "Jung et al. 2022, JAMA Netw Open", "n_cases": 716, "n_controls": 699, "year": 2022, "url": "https://doi.org/10.1001/jamanetworkopen.2022.47162", "pubmed_id": "36520433", "classification": "caveat", "category": "prs", "value_type": "measured", "notes": "Shows partial transferability of a European PRS to East Asians; a trans-ancestry (European + Japanese) meta-analysis PRS was 'slightly' more accurate. AUC not in abstract." }, { "id": "prs-lake2023-colombian-multi-vs-european", "gene": "polygenic", "variant": "Multi-ancestry random-effects PRS vs European-derived PRS", "chromosome": null, "position_hg38": null, "risk_allele": null, "allele_frequency": null, "allele_frequency_source": null, "effect_size": "Maximal AUC 0.79 (multi-ancestry PRS incl. APOE) vs 0.75 (European PRS incl. APOE); 0.68 vs 0.63 excluding APOE", "effect_size_type": "AUC", "odds_ratio": null, "ci_lower": null, "ci_upper": null, "p_value": null, "population": "Colombian three-way admixed cohort: 281 AD cases / 87 neurologically normal controls (TANGL study)", "ancestry": "Hispanic", "study_name": "Lake et al. 2023, Mol Psychiatry", "n_cases": 281, "n_controls": 87, "year": 2023, "url": "https://doi.org/10.1038/s41380-023-02089-w", "pubmed_id": "37198259", "classification": "caveat", "category": "prs", "value_type": "measured", "notes": "Read from PMC10615750. Small test cohort (87 controls); shows that adding even under-powered non-European GWAS improves transfer to admixed populations." }, { "id": "prs-jia2021-chinese-model-auc", "gene": "polygenic", "variant": "4-13 SNP predictive models + APOE e4 status (Chinese GWAS)", "chromosome": null, "position_hg38": null, "risk_allele": null, "allele_frequency": null, "allele_frequency_source": null, "effect_size": "Peak AUC 0.73 (95% CI 0.71-0.74); range 0.63-0.73 across 11 models; validated in a longitudinal cohort of 5,474", "effect_size_type": "AUC", "odds_ratio": null, "ci_lower": null, "ci_upper": null, "p_value": null, "population": "Chinese two-stage GWAS 3,913 cases / 7,593 controls; validation cohort 5,474", "ancestry": "East-Asian", "study_name": "Jia et al. 2021, Brain", "n_cases": 3913, "n_controls": 7593, "year": 2021, "url": "https://doi.org/10.1093/brain/awaa364", "pubmed_id": "33188687", "classification": "caveat", "category": "prs", "value_type": "measured", "notes": "Few-SNP models rather than genome-wide PRS; AUC is dominated by APOE." }, { "id": "prs-caveat-martin2019-ancestry-disparity", "gene": "polygenic", "variant": "PRS accuracy by ancestry (all traits)", "chromosome": null, "position_hg38": null, "risk_allele": null, "allele_frequency": null, "allele_frequency_source": null, "effect_size": "PRS 'available today are several times more accurate in individuals of European ancestry than other ancestries' -- 'an inescapable consequence of Eurocentric biases in GWAS'", "effect_size_type": "qualitative statement (quantified in paper figures, not loaded)", "odds_ratio": null, "ci_lower": null, "ci_upper": null, "p_value": null, "population": "Cross-trait analysis (not AD-specific)", "ancestry": "multi", "study_name": "Martin et al. 2019, Nat Genet", "n_cases": null, "n_controls": null, "year": 2019, "url": "https://doi.org/10.1038/s41588-019-0379-x", "pubmed_id": "30926966", "classification": "caveat", "category": "prs", "value_type": "measured", "notes": "The core transferability caveat: clinical use of current PRS 'would systematically afford greater improvement for European-descent populations'." }, { "id": "gwas-catalog-ad-ancestry-census-2026-09-22", "gene": "all AD GWAS", "variant": "ancestry composition of discovery samples", "chromosome": null, "position_hg38": null, "risk_allele": null, "allele_frequency": null, "allele_frequency_source": null, "effect_size": "European-only discovery samples: 121 of 240 AD GWAS studies; by individuals 66.3% European, 25.1% ancestry not reported, 3.2% single non-European groups (African American/Afro-Caribbean 1.8%, East Asian 0.7%, Hispanic/Latin American 0.6%), 5.4% multi-ancestry entries", "effect_size_type": "percentage of discovery-stage individuals (computed)", "odds_ratio": null, "ci_lower": null, "ci_upper": null, "p_value": null, "population": "All 240 GWAS Catalog studies mapped to MONDO_0004975 (Alzheimer disease) or child terms, initial-stage ancestry entries, total 39,836,379 individual-entries", "ancestry": "multi", "study_name": "GWAS Catalog REST API v2 (EBI), queried 2026-09-22", "n_cases": null, "n_controls": null, "year": 2026, "url": "https://www.ebi.ac.uk/gwas/rest/api/v2/studies?efo_id=MONDO_0004975&show_child_traits=true", "pubmed_id": null, "classification": "caveat", "category": "caveat", "value_type": "computed from catalog metadata (individuals are double-counted across overlapping meta-analyses; 'NR' is dominated by large biobank studies whose ancestry was not curated)", "notes": "Quantifies the European-ancestry skew of the AD GWAS evidence base. Because meta-analyses reuse the same cohorts (IGAP, ADGC, UK Biobank), the individual counts are not unique people; the study-count measure is more robust. Raw per-study rows are in genetics_gwas_ancestry_census.csv." }, { "id": "sirugo2019-missing-diversity", "gene": "all human GWAS", "variant": "European bias in genetic association studies", "chromosome": null, "position_hg38": null, "risk_allele": null, "allele_frequency": null, "allele_frequency_source": null, "effect_size": "'The majority of studies of genetic association with disease have been performed in Europeans' with 'important implications for risk prediction of diseases across global populations'", "effect_size_type": "qualitative (abstract)", "odds_ratio": null, "ci_lower": null, "ci_upper": null, "p_value": null, "population": "All GWAS", "ancestry": "multi", "study_name": "Sirugo, Williams & Tishkoff 2019, Cell", "n_cases": null, "n_controls": null, "year": 2019, "url": "https://doi.org/10.1016/j.cell.2019.02.048", "pubmed_id": "30901543", "classification": "caveat", "category": "caveat", "value_type": "measured", "notes": "Numeric percentages in this commentary were in figures not loaded; see the GWAS Catalog census record for AD-specific numbers computed today." }, { "id": "app-autosomal-dominant-alzforum-2026", "gene": "APP", "variant": "61 variants classified 'AD : Pathogenic' + 9 'Likely Pathogenic' (155 entries total, 18 uncertain significance)", "chromosome": "21", "position_hg38": null, "risk_allele": "heterozygous pathogenic mutation (autosomal dominant)", "allele_frequency": null, "allele_frequency_source": null, "effect_size": "Autosomal dominant, typically early-onset, near-complete penetrance for pathogenic variants (Alzforum classification)", "effect_size_type": "Mendelian inheritance (count of catalogued pathogenic variants)", "odds_ratio": null, "ci_lower": null, "ci_upper": null, "p_value": null, "population": "Families worldwide catalogued by Alzforum (curation as of page load 2026-09-22)", "ancestry": "multi", "study_name": "Alzforum Mutations Database", "n_cases": null, "n_controls": null, "year": 2026, "url": "https://www.alzforum.org/mutations/app", "pubmed_id": null, "classification": "causal", "category": "causal", "value_type": "count of curated database entries (not a measured effect size)", "notes": "Includes duplications and the Swedish/Arctic/Iberian etc. missense mutations; APP triplication in Down syndrome (trisomy 21) is the commonest genetic cause of AD pathology (not counted here). The Icelandic A673T variant is protective (listed on the same page, not counted as pathogenic). Counts were made by string-matching the classification column of the Alzforum table as rendered on 2026-09-22 and may differ slightly from the site's own totals." }, { "id": "psen1-autosomal-dominant-alzforum-2026", "gene": "PSEN1", "variant": "192 variants classified 'AD : Pathogenic' + 100 'Likely Pathogenic' (400 entries total, 39 uncertain significance)", "chromosome": "14", "position_hg38": null, "risk_allele": "heterozygous pathogenic mutation (autosomal dominant)", "allele_frequency": null, "allele_frequency_source": null, "effect_size": "Autosomal dominant, typically early-onset, near-complete penetrance for pathogenic variants (Alzforum classification)", "effect_size_type": "Mendelian inheritance (count of catalogued pathogenic variants)", "odds_ratio": null, "ci_lower": null, "ci_upper": null, "p_value": null, "population": "Families worldwide catalogued by Alzforum (curation as of page load 2026-09-22)", "ancestry": "multi", "study_name": "Alzforum Mutations Database", "n_cases": null, "n_controls": null, "year": 2026, "url": "https://www.alzforum.org/mutations/psen-1", "pubmed_id": null, "classification": "causal", "category": "causal", "value_type": "count of curated database entries (not a measured effect size)", "notes": "Most common cause of autosomal-dominant AD; E280A (Paisa mutation, Colombia) is the largest single kindred. Counts were made by string-matching the classification column of the Alzforum table as rendered on 2026-09-22 and may differ slightly from the site's own totals." }, { "id": "psen2-autosomal-dominant-alzforum-2026", "gene": "PSEN2", "variant": "5 variants classified 'AD : Pathogenic' + 17 'Likely Pathogenic' (97 entries total, 26 uncertain significance)", "chromosome": "1", "position_hg38": null, "risk_allele": "heterozygous pathogenic mutation (autosomal dominant)", "allele_frequency": null, "allele_frequency_source": null, "effect_size": "Autosomal dominant, typically early-onset, near-complete penetrance for pathogenic variants (Alzforum classification)", "effect_size_type": "Mendelian inheritance (count of catalogued pathogenic variants)", "odds_ratio": null, "ci_lower": null, "ci_upper": null, "p_value": null, "population": "Families worldwide catalogued by Alzforum (curation as of page load 2026-09-22)", "ancestry": "multi", "study_name": "Alzforum Mutations Database", "n_cases": null, "n_controls": null, "year": 2026, "url": "https://www.alzforum.org/mutations/psen-2", "pubmed_id": null, "classification": "causal", "category": "causal", "value_type": "count of curated database entries (not a measured effect size)", "notes": "Rarest of the three; Volga German N141I founder mutation; more variable penetrance/onset. Counts were made by string-matching the classification column of the Alzforum table as rendered on 2026-09-22 and may differ slightly from the site's own totals." } ]