Genome-wide association study of PR interval

Arne Pfeufer, Charlotte Van Noord, Kristin D. Marciante, Dan E. Arking, Martin G. Larson, Albert Vernon Smith, Kirill V. Tarasov, Martina Müller, Nona Sotoodehnia, Moritz F. Sinner, Germaine C. Verwoert, Man Li, W. H.Linda Kao, Anna Köttgen, Josef Coresh, Joshua C. Bis, Bruce M. Psaty, Kenneth Rice, Jerome I. Rotter, Fernando RivadeneiraAlbert Hofman, Jan A. Kors, Bruno H.C. Stricker, André G. Uitterlinden, Cornelia M. Van Duijn, Britt M. Beckmann, Wiebke Sauter, Christian Gieger, Steven A. Lubitz, Christopher Newton-Cheh, Thomas J. Wang, Jared W. Magnani, Renate B. Schnabel, Mina K. Chung, John Barnard, Jonathan D. Smith, David R. Van Wagoner, Ramachandran S. Vasan, Thor Aspelund, Gudny Eiriksdottir, Tamara B. Harris, Lenore J. Launer, Samer S. Najjar, Edward Lakatta, David Schlessinger, Manuela Uda, Gonçalo R. Abecasis, Bertram Müller-Myhsok, Georg B. Ehret, Eric Boerwinkle, Aravinda Chakravarti, Elsayed Z. Soliman, Kathryn L. Lunetta, Siegfried Perz, H. Erich Wichmann, Thomas Meitinger, Daniel Levy, Vilmundur Gudnason, Patrick T. Ellinor, Serena Sanna, Stefan Kääb, Jacqueline C.M. Witteman, Alvaro Alonso, Emelia J. Benjamin, Susan R. Heckbert

Research output: Contribution to journalArticle

Abstract

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 × 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.

Original languageEnglish (US)
Pages (from-to)153-159
Number of pages7
JournalNature genetics
Volume42
Issue number2
DOIs
StatePublished - Feb 1 2010

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ASJC Scopus subject areas

  • Genetics

Cite this

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., ... Heckbert, S. R. (2010). Genome-wide association study of PR interval. Nature genetics, 42(2), 153-159. https://doi.org/10.1038/ng.517