The genetic background of atrial fibrillation (AF) in whites and African Americans is largely unknown. Genes in cardiovascular pathways have not been systematically investigated.
Methods and Results
We examined a panel of approximately 50,000 common single nucleotide polymorphisms (SNPs) in 2,095 cardiovascular candidate genes and AF in three cohorts with participants of European (n=18,524; 2,260 cases) or African American descent (n=3,662; 263 cases) in the National Heart Lung and Blood Institute's Candidate Gene Association Resource. Results in whites were followed up in the German Competence Network for AF (n=906, 468 cases). The top result was assessed in relation to incident ischemic stroke in the Cohorts for Heart and Aging Research in Genomic Epidemiology Stroke Consortium (n= 19,602 whites, 1544 incident strokes). SNP rs4845625 in the IL6R gene was associated with AF (relative risk (RR) C allele, 0.90; 95% confidence interval (CI), 0.85–0.95; P=0.0005) in whites, but did not reach statistical significance in African Americans (RR, 0.86; 95% CI, 0.72–1.03; P=0.09). The results were comparable in the German AF Network replication, (RR, 0.71; 95% CI, 0.57–0.89; P=0.003). No association between rs4845625 and stroke was observed in whites. The known chromosome 4 locus near PITX2 in whites also was associated with AF in African Americans (rs4611994, hazard ratio, 1.40; 95% CI, 1.16–1.69; P=0.0005).
In a community-based cohort meta-analysis, we identified genetic association in IL6R with AF in whites. Additionally, we demonstrated that the chromosome 4 locus known from recent genome-wide association studies in whites is associated with AF in African Americans.
Keywords: atrial fibrillation, single nucleotide polymorphism, epidemiology, cohort study, race/ethnicity