Meta-analysis identifies six new susceptibility loci for atrial fibrillation

Abstract

Atrial fibrillation is a highly prevalent arrhythmia and a major risk factor for stroke, heart failure and death. We conducted a genome-wide association study (GWAS) in individuals of European ancestry, including 6,707 with and 52,426 without atrial fibrillation. Six new atrial fibrillation susceptibility loci were identified and replicated in an additional sample of individuals of European ancestry, including 5,381 subjects with and 10,030 subjects without atrial fibrillation (P < 5 × 10(-8)). Four of the loci identified in Europeans were further replicated in silico in a GWAS of Japanese individuals, including 843 individuals with and 3,350 individuals without atrial fibrillation. The identified loci implicate candidate genes that encode transcription factors related to cardiopulmonary development, cardiac-expressed ion channels and cell signaling molecules.

Figure 1

Manhattan plot of meta-analysis results for genome-wide association with atrial fibrillation. The −log₁₀ (P value) is plotted against the physical position of each SNP on each chromosome. The threshold for genome-wide significance, P < 5 × 10⁻⁸, is indicated by the dashed line. The three previously reported loci for atrial fibrillation are indicated in blue, and the seven new loci that exceeded the genome-wide significance threshold are indicated in orange.

Figure 2

Regional plots for seven new atrial fibrillation loci in the discovery sample with P < 1 × 10⁻⁸. SNPs are plotted by meta-analysis P value and genomic position (NCBI Build 36). The SNP of interest is labeled. The strength of LD is indicated by red coloring. Estimated recombination rates are shown by the blue peaks, and gene annotations are indicated by dark green arrows. LD and recombination rates are based on the Utah residents of Northern and Western European ancestry (CEU) HapMap cohort (release 22). Plots were prepared using SNAP.