ArticleAlzheimer's research & therapy2025
Genome-wide association studies of Alzheimer's disease and related disorders stratified by sex, onset age, and Apolipoprotein E genotype reveal novel risk loci in African Americans.
Article in Alzheimer's research & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Curation of Mini Mental State Examination (MMSE) Scores in the VA Million Veteran Program (MVP): Applications for Cognitive Aging Research.medRxiv : the preprint server for health sciences · 2026Article
- HiFiMAP: High-resolution fast identity-by-descent mapping test.medRxiv : the preprint server for health sciences · 2026Article
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17 authors.
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Abstract
backgroundAlzheimer's disease (AD) risk variants have been identified in European ancestry cohorts that have stronger effects at certain ages, in individuals with a specific sex, or in those with specific isoforms of APOE, the strongest AD risk locus. However, sample sizes in African ancestry (AA) cohorts have been underpowered to perform stratified analyses.
methodsWe generated genome-wide association study datasets stratified by sex, age at onset (< 75 vs ≥ 75), and APOE-ε4 carrier status in AA cohorts from MVP and the Alzheimer's Disease Genetics Consortium (ADGC). Outcomes in MVP were AD and related dementias (ADRD; n = 4073 cases and 19,648 controls) and proxy dementia (i.e., reported dementia in a parent, n = 6216 cases and 21,566 controls) while ADGC analyses examined AD (n = 2425 cases and 5069 controls). The proxy dementia GWASs were included in the sex-stratified meta-analysis corresponding to the sex of the affected parent. The top genes were tested for differential expression in AA brain tissue.
resultsIn addition to the APOE region, genome-wide significant associations were observed in an intergenic region near the EPHA5 gene (rs141838133, p = 2.19 × 10
conclusionsAge, sex, and APOE-stratified analyses of dementia in AA participants from two cohorts revealed potential new associations. Stratified analyses may yield critical information about the genetic heterogeneity underlying dementia risk and lead to advances in precision medicine.
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