Journal
NATURE GENETICS
Volume 42, Issue 2, Pages 153-U89Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.517
Keywords
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Categories
Funding
- US National Institutes of Health [N01-AG-12100]
- US National Institute on Aging (NIA)
- Hjartavernd (Icelandic Heart Association)
- Althingi (Icelandic parliament)
- US National Heart, Lung, and Blood Institute (NHLBI)
- US National Eye Institute
- US National Institute on Deafness and Other Communication Disorders
- NHLBI [N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55022, R01-HL-087641, R01-HL-59367, R01-HL-086694, R01-HL-054512, R01-HL090620, P50-HL077107, N01-HC85079, N01-HC-85086, N01-HC-35129, N01-HC-15103, N01-HC-55222, N01-HC-75150, N01-HC-45133, U01-HL-080295, R01-HL-087652]
- US National Human Genome Research Institute (NHGRI) [U01-HG004402]
- NIH [HHSN268200625226C, UL1-RR025005, N01-HC-25195, HL-076784, AG-028321, N01-HC25195, HL-080025, 6R01-NS-17950]
- Donald W. Reynolds Cardiovascular Clinical Research Center
- Heart and Vascular Institute, Department of Cardiovascular Medicine, Cleveland Clinic
- US National Center for Research Resources [M01-RR-00425]
- National Institute of Diabetes and Digestive and Kidney Diseases [DK063491]
- US National Institute of Neurological Disorders and Stroke
- Cedars-Sinai Board of Governors
- Boston University School of Medicine and Boston Medical Center (LINGA-II)
- Robert Dawson Evans Endowment
- Doris Duke Charitable Foundation
- Deutsche Forschungsgemeinschaft [SCHN 1149/1-1]
- Pfizer
- Bundesministerium fur Bildung und Forschung Nationales Genomforschungsnetz
- Leducq Foundation [07-03 Ludvig 03]
- Ludwig-Maximilians University (LMU) [FuFoLe 557/569]
- Helmholtz Zentrum Munchen fur Gesundheit und Umwelt
- The Netherlands Organisation for Scientific Research [175.010.2005.011, 911.03.012, 050-060-810]
- European Commission
- Erasmus Medical Center, Erasmus University Rotterdam
- NIA [NO1-AG-1-2109, 263-MA-410953]
- [01-GS-0499]
- [01-GR-0103]
- [01-GR-0803]
- [AFNET 01-GI-0204 01-GS-0838]
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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.
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