Genome-wide association study of PR interval

A Pfeufer, Charlotte Noord, KD Marciante, DE Arking, MG Larson, AV Smith, KV Tarasov, M (Majon) Muller, N Sotoodehnia, MF Sinner, Germaine Verwoert, M Li, WHL Kao, A Kottgen, J Coresh, JC Bis, BM Psaty, K Rice, JI Rotter, Fernando RivadeneiraBert Hofman, Jan Kors, Bruno Stricker, André Uitterlinden, Cornelia Duijn, BM Beckmann, W Sauter, C Gieger, SA Lubitz, C Newton-Cheh, TJ Wang, JW Magnani, RB Schnabel, MK Chung, J Barnard, JD Smith, DR Van Wagoner, RS Vasan, T Aspelund, G Eiriksdottir, TB Harris, LJ (Lenore) Launer, SS Najjar, E Lakatta, D Schlessinger, M Uda, GR Abecasis, B Muller-Myhsok, GB Ehret, E Boerwinkle, A Chakravarti, EZ Soliman, KL Lunetta, S Perz, HE Wichmann, T Meitinger, D Levy, V Gudnason, PT Ellinor, S Sanna, S Kaab, JCM Witteman, A Alonso, EJ Benjamin, SR Heckbert

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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-nalysis 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, NKX25 (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 languageUndefined/Unknown
Pages (from-to)153-U89
JournalNature Genetics
Volume42
Issue number2
DOIs
Publication statusPublished - 2010

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