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Genome-wide association study of PR interval.

TitleGenome-wide association study of PR interval.
Publication TypeJournal Article
Year of Publication2010
AuthorsPfeufer, A, van Noord, C, Marciante, KD, Arking, DE, Larson, MG, Smith, AVernon, Tarasov, KV, Müller, M, Sotoodehnia, N, Sinner, MF, Verwoert, GC, Li, M, Kao, LWH, Köttgen, A, Coresh, J, Bis, JC, Psaty, BM, Rice, K, Rotter, JI, Rivadeneira, F, Hofman, A, Kors, JA, Stricker, BHC, Uitterlinden, AG, van Duijn, CM, Beckmann, BM, Sauter, W, Gieger, C, Lubitz, SA, Newton-Cheh, C, Wang, TJ, Magnani, JW, Schnabel, RB, Chung, MK, Barnard, J, Smith, JD, Van Wagoner, DR, Vasan, RS, Aspelund, T, Eiriksdottir, G, Harris, TB, Launer, LJ, Najjar, SS, Lakatta, E, Schlessinger, D, Uda, M, Abecasis, GR, Müller-Myhsok, B, Ehret, GB, Boerwinkle, E, Chakravarti, A, Soliman, EZ, Lunetta, KL, Perz, S, Wichmann, H-E, Meitinger, T, Levy, D, Gudnason, V, Ellinor, PT, Sanna, S, Kääb, S, Witteman, JCM, Alonso, A, Benjamin, EJ, Heckbert, SR
JournalNat Genet
Volume42
Issue2
Pagination153-9
Date Published2010 Feb
ISSN1546-1718
KeywordsAged, Atrial Fibrillation, Cohort Studies, Electrocardiography, Female, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Heart Conduction System, Humans, Male, Meta-Analysis as Topic
Abstract<p>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.</p>
DOI10.1038/ng.517
Alternate JournalNat. Genet.
PubMed ID20062060
PubMed Central IDPMC2850197
Grant ListHL-076784 / HL / NHLBI NIH HHS / United States
K23 HL080025-05 / HL / NHLBI NIH HHS / United States
P50-HL077107 / HL / NHLBI NIH HHS / United States
U01-HG004402 / HG / NHGRI NIH HHS / United States
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