Genome-wide association identifies the first risk loci for psychosis in Alzheimer disease
DeMichele-Sweet MAA, Klei L, Creese B, Harwood JC, Weamer EA, McClain L, Sims R, Hernandez I et al.. Molecular psychiatry, 2021-06-10
Topic: Amyloid, tau and blood-test diagnosis
Plain-language summary
Psychotic symptoms, defined as the occurrence of delusions or hallucinations, are frequent in Alzheimer disease (AD with psychosis, AD + P). AD + P affects ~50% of individuals with AD, identifies a subgroup with poor outcomes, and is associated with a greater degree of cognitive impairment and depressive symptoms, compared to subjects without psychosis (AD - P). Although the estimated heritability of AD + P is 61%, genetic sources of risk are unknown. We report a genome-wide meta-analysis of 12,317 AD subjects, 5445 AD + P. Results showed common genetic variation accounted for a significant portion of heritability. Two loci, one in ENPP6 (rs9994623, O.R. (95%CI) 1.16 (1.10, 1.22), p = 1.26 × 10 -8 ) and one spanning the 3'-UTR of an alternatively spliced transcript of SUMF1 (rs201109606, O.R. 0.65 (0.56-0.76), p = 3.24 × 10 -8 ), had genome-wide significant associations with AD + P. Gene-based analysis identified a significant association with APOE, due to the APOE risk haplotype ε4. AD + P demonstrated negative genetic correlations with cognitive and educational attainment and positive genetic correlation with depressive symptoms. We previously observed a negative genetic correlation with schizophrenia; instead, we now found a stronger negative correlation with the related phenotype of bipolar disorder. Analysis of polygenic risk scores supported this genetic correlation and documented a positive genetic correlation with risk variation for AD, beyond the effect of ε4. We also document a small set of SNPs likely to affect risk for AD + P and AD or schizophrenia. These findings provide the first unbiased identification of the association of psychosis in AD with common genetic variation and provide insights into its genetic architecture.
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APA 7th
DeMichele-Sweet, M. A. A., Klei, L., Creese, B., Harwood, J. C., Weamer, E. A., McClain, L., et al. (2021). Genome-wide association identifies the first risk loci for psychosis in Alzheimer disease. Molecular psychiatry. https://doi.org/10.1038/s41380-021-01152-8
Vancouver
DeMichele-Sweet MAA, Klei L, Creese B, Harwood JC, Weamer EA, McClain L, et al. Genome-wide association identifies the first risk loci for psychosis in Alzheimer disease. Molecular psychiatry. 2021. doi:10.1038/s41380-021-01152-8. PMID: 34112972.
BibTeX
@article{demichelesweet2021-34112972,
author = {DeMichele-Sweet, M. A. A. and Klei, L. and Creese, B. and Harwood, J. C. and Weamer, E. A. and McClain, L. and Sims, R. and Hernandez, I. and others},
title = {{Genome-wide association identifies the first risk loci for psychosis in Alzheimer disease}},
journal = {Molecular psychiatry},
year = {2021},
doi = {10.1038/s41380-021-01152-8},
pmid = {34112972},
url = {https://doi.org/10.1038/s41380-021-01152-8}
}
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Key findings
- AD + P affects ~50% of individuals with AD, identifies a subgroup with poor outcomes, and is associated with a greater degree of cognitive impairment and depressive symptoms, compared to subjects without psychosis (AD - P).
- Results showed common genetic variation accounted for a significant portion of heritability.
- (95%CI) 1.16 (1.10, 1.22), p = 1.26 × 10 -8 ) and one spanning the 3'-UTR of an alternatively spliced transcript of SUMF1 (rs201109606, O.R. 0.65 (0.56-0.76), p = 3.24 × 10 -8 ), had genome-wide significant associations with AD + P.
- Gene-based analysis identified a significant association with APOE, due to the APOE risk haplotype ε4.
- AD + P demonstrated negative genetic correlations with cognitive and educational attainment and positive genetic correlation with depressive symptoms.
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Study details
- Study designmeta-analysis
- Evidence strengthHigh
How this study scored 74/100
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 and multicenter collaboration, so those were left out: it earned 43 of the 58 points we could judge it on, which is 74 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 | 2021 — 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) |
| Randomized / blinded | 0 / 2 | A review of other studies — randomization 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 |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 34112972) |
| Free to read | 2 / 2 | Free to read |
| Points | 43 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 43 of the 58 points we could judge it on is 74 out of 100. |
| Total | 74 / 100 | — |
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