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Pfeufer, A. ; van Noord, C.* ; Marciante, K.D.* ; Arking, D.E.* ; Larson, M.G.* ; Smith, A.V.* ; Tarasov, K.V.* ; Müller, M. ; Sotoodehnia, N.* ; Sinner, M.F.* ; Verwoert, G.C.* ; Li, M.* ; Kao, W.H.L.* ; Köttgen, A.* ; Coresh, J.* ; Bis, J.C.* ; Psaty, B.M.* ; Rice, K.* ; Rotter, J.I.* ; Rivadeneira, F. ; Hofman, A.* ; Kors, J.A.* ; Stricker, B.H.C.* ; Uitterlinden, A.G.* ; van Duijn, C.M.* ; Beckmann, B.M.* ; Sauter, W. ; Gieger, C. ; Lubitz, S.A.* ; Newton-Cheh, C.* ; Wang, T.J.* ; Magnani, J.W.* ; Schnabel, R.B.* ; Chung, M.K.* ; Barnard, J.* ; Smith, J.D.* ; van Wagoner, D.R.* ; Vasan, R.S.* ; Aspelund, T.* ; Eiriksdottir, G.* ; Harris, T.B.* ; Launer, L.J.* ; Najjar, S.S.* ; Lakatta, E.* ; Schlessinger, D.* ; Uda, M.* ; Abecasis, G.R.* ; Müller-Myhsok, B.* ; Ehret, G.B.* ; Boerwinkle, E.* ; Chakravarti, A.* ; Soliman, E.Z.* ; Lunetta, K.L.* ; Perz, S. ; Wichmann, H.-E. ; Meitinger, T. ; Levy, D.* ; Gudnason, V.* ; Ellinor, P.T.* ; Sanna, S.* ; Kääb, S.* ; Witteman, J.C.M.* ; Alonso, A.* ; Benjamin, E.J.* ; Heckbert, S.R.*

Genome-wide association study of PR interval.

Nat. Genet. 42, 153-159 (2010)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
The electrocardiographic PR interval (or PQ interval) reflects atrial and atrioventricular nodal conduction, disturbances of which increase risk of atrial fibrillation. We report a meta-analysis of genome-wide association studies for PR interval from seven population-based European studies in the CHARGE Consortium: AGES, ARIC, CHS, FHS, KORA, Rotterdam Study, and SardiNIA (N = 28,517). We identified nine loci associated with PR interval at P < 5 x 10(-8). At the 3p22.2 locus, we observed two independent associations in voltage-gated sodium channel genes, SCN10A and SCN5A. Six of the loci were near cardiac developmental genes, including CAV1-CAV2, NKX2-5 (CSX1), SOX5, WNT11, MEIS1, and TBX5-TBX3, providing pathophysiologically interesting candidate genes. Five of the loci, SCN5A, SCN10A, NKX2-5, CAV1-CAV2, and SOX5, were also associated with atrial fibrillation (N = 5,741 cases, P < 0.0056). This suggests a role for common variation in ion channel and developmental genes in atrial and atrioventricular conduction as well as in susceptibility to atrial fibrillation.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Atrial-fibrillation; Common variants; Sodium-channel; Heart-rate; Atherosclerosis risk; National heart; System; Design; Individuals; Variability
ISSN (print) / ISBN 1061-4036
e-ISSN 1546-1718
Journal Nature Genetics
Quellenangaben Volume: 42, Issue: 2, Pages: 153-159 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place New York, NY
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology (EPI)
Institute of Human Genetics (IHG)
Institute of Biological and Medical Imaging (IBMI)