Variants in ZFHX3 are associated with atrial fibrillation in individuals of European ancestry

Abstract

We conducted meta-analyses of genome-wide association studies for atrial fibrillation (AF) in participants from five community-based cohorts. Meta-analyses of 896 prevalent (15,768 referents) and 2,517 incident (21,337 referents) AF cases identified a new locus for AF (ZFHX3, rs2106261, risk ratio RR = 1.19; P = 2.3 x 10(-7)). We replicated this association in an independent cohort from the German AF Network (odds ratio = 1.44; P = 1.6 x 10(-11); combined RR = 1.25; combined P = 1.8 x 10(-15)).

Figure 1. Regional association plots for signal loci on chromosomes 4, 16 and 1

At each SNP location (genomic position, NCBI Build 36) we plot the log₁₀ P value from combined analysis of incident and prevalent AF. Symbol colors indicate the strength of linkage disequilibrium derived from CEU HapMap build 22: strong (red, r²≥0.8) moderate (orange, 0.5≤r²<0.8) weak (yellow, 0.20≤r²<0.5) and low (white, r²<0.2). Estimated recombination rates are represented by pale blue lines and gene annotations by dark green arrows.

Figure 1. Regional association plots for signal loci on chromosomes 4, 16 and 1

At each SNP location (genomic position, NCBI Build 36) we plot the log₁₀ P value from combined analysis of incident and prevalent AF. Symbol colors indicate the strength of linkage disequilibrium derived from CEU HapMap build 22: strong (red, r²≥0.8) moderate (orange, 0.5≤r²<0.8) weak (yellow, 0.20≤r²<0.5) and low (white, r²<0.2). Estimated recombination rates are represented by pale blue lines and gene annotations by dark green arrows.

Figure 1. Regional association plots for signal loci on chromosomes 4, 16 and 1

At each SNP location (genomic position, NCBI Build 36) we plot the log₁₀ P value from combined analysis of incident and prevalent AF. Symbol colors indicate the strength of linkage disequilibrium derived from CEU HapMap build 22: strong (red, r²≥0.8) moderate (orange, 0.5≤r²<0.8) weak (yellow, 0.20≤r²<0.5) and low (white, r²<0.2). Estimated recombination rates are represented by pale blue lines and gene annotations by dark green arrows.