Inferring the Molecular Mechanisms of Noncoding Alzheimer's Disease-Associated Genetic Variants.

ABSTRACT: Most of the loci identified by genome-wide association studies (GWAS) for late-onset Alzheimer's disease (LOAD) are in strong linkage disequilibrium (LD) with nearby variants all of which could be the actual functional variants, often in non-protein-coding regions and implicating underlying gene regulatory mechanisms. We set out to characterize the causal variants, regulatory mechanisms, tissue contexts, and target genes underlying these associations. We applied our INFERNO algorithm to the top 19 non-APOE loci from the IGAP GWAS study. INFERNO annotated all LD-expanded variants at each locus with tissue-specific regulatory activity. Bayesian co-localization analysis of summary statistics and eQTL data was performed to identify tissue-specific target genes. INFERNO identified enhancer dysr

SUBMITTER: Amlie-Wolf A 

PROVIDER: S-EPMC7316086 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature