Large-Scale Candidate Gene Analysis in Whites and African Americans Identifies IL6R Polymorphism in Relation to Atrial Fibrillation The National Heart, Lung, and Blood Institute's Candidate Gene Association Resource (CARe) project

Renate B. Schnabel*, Kathleen F. Kerr, Steven A. Lubitz, Ermeg L. Alkylbekova, Gregory M. Marcus, Moritz F. Sinner, Jared W. Magnani, Philip A. Wolf, Rajat Deo, Donald M. Lloyd-Jones, Kathryn L. Lunetta, Reena Mehra, Daniel Levy, Ervin R. Fox, Dan E. Arking, Thomas H. Mosley, Martina Müller-Nurasyid, Taylor R. Young, H. Erich Wichmann, Sudha SeshadriDeborah N. Farlow, Jerome I. Rotter, Elsayed Z. Soliman, Nicole L. Glazer, James G. Wilson, Monique M B Breteler, Nona Sotoodehnia, Christopher Newton-Cheh, Stefan Kääb, Patrick T. Ellinor, Alvaro Alonso, Emelia J. Benjamin, Susan R. Heckbert

*Corresponding author for this work

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

Background-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 2095 cardiovascular candidate genes and AF in 3 cohorts with participants of European (n=18 524; 2260 cases) or African American descent (n=3662; 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). Conclusions-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.

Original languageEnglish (US)
Pages (from-to)557-564
Number of pages8
JournalCirculation: Cardiovascular Genetics
Volume4
Issue number5
DOIs
StatePublished - Oct 2011

Keywords

  • Atrial fibrillation
  • Cohort study
  • Epidemiology
  • Race/ethnicity
  • Single nucleotide polymorphism

ASJC Scopus subject areas

  • Genetics
  • Cardiology and Cardiovascular Medicine
  • Genetics(clinical)

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    Schnabel, R. B., Kerr, K. F., Lubitz, S. A., Alkylbekova, E. L., Marcus, G. M., Sinner, M. F., Magnani, J. W., Wolf, P. A., Deo, R., Lloyd-Jones, D. M., Lunetta, K. L., Mehra, R., Levy, D., Fox, E. R., Arking, D. E., Mosley, T. H., Müller-Nurasyid, M., Young, T. R., Wichmann, H. E., ... Heckbert, S. R. (2011). Large-Scale Candidate Gene Analysis in Whites and African Americans Identifies IL6R Polymorphism in Relation to Atrial Fibrillation The National Heart, Lung, and Blood Institute's Candidate Gene Association Resource (CARe) project. Circulation: Cardiovascular Genetics, 4(5), 557-564. https://doi.org/10.1161/CIRCGENETICS.110.959197