Atrial fibrillation variant-to-gene prioritization through cross-ancestry eQTL and single-nucleus multiomic analyses.

ABSTRACT: Atrial fibrillation (AF) is the most common arrhythmia in the world. Human genetics can provide strong AF therapeutic candidates, but the identification of the causal genes and their functions remains challenging. Here, we applied an AF fine-mapping strategy that leverages results from a previously published cross-ancestry genome-wide association study (GWAS), expression quantitative trait loci (eQTLs) from left atrial appendages (LAAs) obtained from two cohorts with distinct ancestry, and a paired RNA sequencing (RNA-seq) and ATAC sequencing (ATAC-seq) LAA single-nucleus assay (sn-multiome). At nine AF loci, our co-localization and fine-mapping analyses implicated 14 genes. Data integration identified several candidate causal AF variants, including rs7612445 at GNB4 and rs242557 at

SUBMITTER: Leblanc FJA 

PROVIDER: S-EPMC11388022 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature