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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. ; Seshadri, S* ; Farlow, D.N.* ; Rotter, J.I.* ; Soliman, E.Z.* ; Glazer, N.L.* ; Wilson, J.G.* ; Breteler, M.M.* ; Sotoodehnia, N.* ; Newton-Cheh, C.* ; Kääb, S.* ; Ellinor, P.T.* ; Alonso, A.* ; Benjamin, E.J.* ; Heckbert, S.R* ; CARE Consortium (*)

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.

Circ. Cardiovasc. Genet. 4, 557-564 (2011)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter atrial fibrillation; single nucleotide polymorphism; epidemiology; cohort study; race/ethnicity
ISSN (print) / ISBN 1942-325X
e-ISSN 1942-3268
Zeitschrift Circulation: Cardiovascular Genetics
Quellenangaben Band: 4, Heft: 5, Seiten: 557-564 Artikelnummer: , Supplement: ,
Verlag Lippincott Williams & Wilkins
Verlagsort Hagerstown, Md
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Genetic Epidemiology (IGE)