Abstract 14052: Feasibility of Whole Genome Sequencing for Atrial Fibrillation

Background: Genome-wide association studies (GWAS) have identified 14 loci associated with atrial fibrillation (AF). Whole genome sequencing (WGS) may enable the identification of causal variation underlying AF through greater variant ascertainment than with genotyping arrays. We report interim results for a subset of the NHLBI Trans-Omics for Precision Medicine WGS Program, in which ~3000 individuals with early-onset AF (onset ≤65 years of age) and 4000 referent individuals will be sequenced. Methods: In the current freeze, 1423 individuals with early-onset AF from 9 studies and 1431 referent individuals from the Framingham Heart Study underwent WGS at the Broad Institute (Cambridge, MA) and passed quality control filters. Variants were jointly called at the University of Michigan. European ancestry was verified using principal components. Common variants (≥5%) were tested for association with AF after age- and sex-adjustment. Low-frequency and rare variants were grouped in regions of interest and tested...