Multi-ancestry meta-analysis and fine-mapping in Alzheimer's disease
Julie Lake, Caroline Warly Solsberg, Jonggeol Jeffrey Kim, Juliana Acosta-Uribe, Mary B Makarious, Zizheng Li, Kristin Levine, Peter Heutink et al.. Molecular psychiatry, 2023-05-18
Topic: Genetics and APOE
Genome-wide association studies (GWAS) of Alzheimer's disease are predominantly carried out in European ancestry individuals despite the known variation in genetic architecture and disease prevalence across global populations. We leveraged published GWAS summary statistics from European, East Asian, and African American populations, and an additional GWAS from a Caribbean Hispanic population using previously reported genotype data to perform the largest multi-ancestry GWAS meta-analysis of Alzheimer's disease and related dementias to date. This method allowed us to identify two independent novel disease-associated loci on chromosome 3. We also leveraged diverse haplotype structures to fine-map nine loci with a posterior probability >0.8 and globally assessed the heterogeneity of known risk factors across populations. Additionally, we compared the generalizability of multi-ancestry- and single-ancestry-derived polygenic risk scores in a three-way admixed Colombian population. Our findings highlight the importance of multi-ancestry representation in uncovering and understanding putative factors that contribute to risk of Alzheimer's disease and related dementias.
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APA 7th
Lake, J., Solsberg, C. W., Kim, J. J., Acosta-Uribe, J., Makarious, M. B., Li, Z., et al. (2023). Multi-ancestry meta-analysis and fine-mapping in Alzheimer's disease. Molecular psychiatry. https://doi.org/10.1038/s41380-023-02089-w
Vancouver
Lake J, Solsberg CW, Kim JJ, Acosta-Uribe J, Makarious MB, Li Z, et al. Multi-ancestry meta-analysis and fine-mapping in Alzheimer's disease. Molecular psychiatry. 2023. doi:10.1038/s41380-023-02089-w. PMID: 37198259.
BibTeX
@article{lake2023-37198259,
author = {Lake, Julie and Solsberg, Caroline Warly and Kim, Jonggeol Jeffrey and Acosta-Uribe, Juliana and Makarious, Mary B and Li, Zizheng and Levine, Kristin and Heutink, Peter and others},
title = {{Multi-ancestry meta-analysis and fine-mapping in Alzheimer's disease}},
journal = {Molecular psychiatry},
year = {2023},
doi = {10.1038/s41380-023-02089-w},
pmid = {37198259},
url = {https://doi.org/10.1038/s41380-023-02089-w}
}
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Key findings
- Our findings highlight the importance of multi-ancestry representation in uncovering and understanding putative factors that contribute to risk of Alzheimer's disease and related dementias.
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Study details
- Study designmeta-analysis
- Evidence strengthHigh
How this study scored 73/100
Published in a leading specialty journal, and it is a meta-analysis pooling many studies. Scored zero for sample size, effect reported and studied in people because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record, multi-centre collaboration and free to read, so those were left out: it earned 41 of the 56 points we could judge it on, which is 73 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Molecular psychiatry) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 12 / 12 | A meta-analysis pooling many studies |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2023 — within 6 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | A review of other studies — randomisation is not credited here |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 37198259) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 41 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 41 of the 56 points we could judge it on is 73 out of 100. |
| Total | 73 / 100 | — |
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