Cross-ancestry genome-wide association study identifies implications of SORL1 in cerebral beta-amyloid deposition.

ABSTRACT: GWAS of Alzheimer's disease have been predominantly based on European ancestry cohorts with clinically diagnosed patients. Increasing the ancestral diversity of GWAS and focusing on imaging brain biomarkers for Alzheimer's disease may lead to the identification of new genetic loci. Here, we perform a GWAS on cerebral β-amyloid deposition measured by PET imaging in 3,885 East Asians and a cross-ancestry GWAS meta-analysis with data from 11,816 European participants. Our GWAS analysis replicates known loci (APOE4, CR1, and FERMT2) and identifies a novel locus near SORL1 that is significantly associated with β-amyloid deposition. Single-nucleus expression analysis shows that SORL1 is differentially expressed according to β-amyloid positivity in microglia. Our joint association analysis using

SUBMITTER: Kim JP 

PROVIDER: S-EPMC11965558 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature