Genome-wide interaction analysis of pathological hallmarks in Alzheimer's disease.

ABSTRACT: Genome-wide association studies have identified many loci associated with Alzheimer's dementia. However, these variants only explain part of the heritability of Alzheimer's disease (AD). As genetic epistasis can be a major contributor to the "missing heritability" of AD, we conducted genome-wide epistasis screening for AD pathologies in 2 independent cohorts. First, we performed a genome-wide epistasis study of AD-related brain pathologies (N_max = 1318) in ROS/MAP. Candidate interactions were validated using cerebrospinal fluid biomarkers of AD in ADNI (N_max = 1128). Further functional analysis tested the association of candidate interactions with neuroimaging phenotypes. For tau and amyloid-β pathology, we identified 2803 and 464 candidate SNP-SNP interactions, respe

SUBMITTER: Wang H 

PROVIDER: S-EPMC9795865 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature