Genome-wide association study of PR interval (original) (raw)

References

1. Havlik, R.J., Garrison, R.J., Fabsitz, R. & Feinleib, M. Variability of heart rate, P-R, QRS and Q-T durations in twins. J. Electrocardiol. 13, 45–48 (1980).
   Article CAS Google Scholar
2. Hanson, B. et al. Genetic factors in the electrocardiogram and heart rate of twins reared apart and together. Am. J. Cardiol. 63, 606–609 (1989).
   Article CAS Google Scholar
3. Pilia, G. et al. Heritability of cardiovascular and personality traits in 6,148 Sardinians. PLoS Genet. 2, e132 (2006).
   Article Google Scholar
4. Newton-Cheh, C. et al. Genome wide association study of electrocardiographic and heart rate variability traits: the Framingham Heart Study. BMC Med. Genet. 8, S7 (2007).
   Article Google Scholar
5. Benjamin, E.J. et al. Prevention of atrial fibrillation: report from a national heart, lung, and blood institute workshop. Circulation 119, 606–618 (2009).
   Article Google Scholar
6. Heeringa, J. et al. Prevalence, incidence and lifetime risk of atrial fibrillation: the Rotterdam study. Eur. Heart J. 27, 949–953 (2006).
   Article Google Scholar
7. Fox, C.S. et al. Parental atrial fibrillation as a risk factor for atrial fibrillation in offspring. J. Am. Med. Assoc. 291, 2851–2855 (2004).
   Article CAS Google Scholar
8. Gudbjartsson, D.F. et al. Variants conferring risk of atrial fibrillation on chromosome 4q25. Nature 448, 353–357 (2007).
   Article CAS Google Scholar
9. Benjamin, E.J. et al. Variants in ZFHX3 are associated with atrial fibrillation in individuals of European ancestry. Nat. Genet. 41, 879–881 (2009).
   Article CAS Google Scholar
10. Sinner, M.F. et al. The non-synonymous coding IKr-channel variant KCNH2–K897T is associated with atrial fibrillation: results from a systematic candidate gene-based analysis of KCNH2 (HERG). Eur. Heart J. 29, 907–914 (2008).
    Article CAS Google Scholar
11. Olsson, S.B., Cotoi, S. & Varnauskas, E. Monophasic action potential and sinus rhythm stability after conversion of atrial fibrillation. Acta Med. Scand. 190, 381–387 (1971).
    Article CAS Google Scholar
12. Soliman, E.Z., Prineas, R.J., Case, L.D., Zhang, Z.M. & Goff, D.C. Jr. Ethnic distribution of ECG predictors of atrial fibrillation and its impact on understanding the ethnic distribution of ischemic stroke in the Atherosclerosis Risk in Communities (ARIC) study. Stroke 40, 1204–1211 (2009).
    Article Google Scholar
13. Cheng, S. et al. Long-term outcomes in individuals with prolonged PR interval or first-degree atrioventricular block. J. Am. Med. Assoc. 301, 2571–2577 (2009).
    Article CAS Google Scholar
14. Schnabel, R.B. et al. Development of a risk score for atrial fibrillation (the Framingham Heart Study): a community-based cohort study. Lancet 373, 739–745 (2009).
    Article Google Scholar
15. Harris, T.B. et al. Age, Gene/Environment Susceptibility-Reykjavik study: multidisciplinary applied phenomics. Am. J. Epidemiol. 165, 1076–1087 (2007).
    Article Google Scholar
16. ARIC Investigators. The Atherosclerosis Risk in Communities (ARIC) study: design and objectives. Am. J. Epidemiol. 129, 687–702 (1989).
17. Fried, L.P. et al. The Cardiovascular Health Study: design and rationale. Ann. Epidemiol. 1, 263–276 (1991).
    Article CAS Google Scholar
18. Splansky, G.L. et al. The Third Generation Cohort of the National Heart, Lung, and Blood Institute's Framingham Heart Study: design, recruitment, and initial examination. Am. J. Epidemiol. 165, 1328–1335 (2007).
    Article Google Scholar
19. Wichmann, H.E., Gieger, C. & Illig, T. KORA-gen–resource for population genetics, controls and a broad spectrum of disease phenotypes. Gesundheitswesen 67, S26–S30 (2005).
    Article Google Scholar
20. Hofman, A. et al. The Rotterdam Study: objectives and design update. Eur. J. Epidemiol. 22, 819–829 (2007).
    Article Google Scholar
21. The International HapMap Consortium. A haplotype map of the human genome. Nature 437, 1299–1320 (2005).
22. Nothnagel, M., Ellinghaus, D., Schreiber, S., Krawczak, M. & Franke, A. A comprehensive evaluation of SNP genotype imputation. Hum. Genet. 125, 163–171 (2009).
    Article CAS Google Scholar
23. Chung, M.K. et al. C-reactive protein elevation in patients with atrial arrhythmias: inflammatory mechanisms and persistence of atrial fibrillation. Circulation 104, 2886–2891 (2001).
    Article CAS Google Scholar
24. Devlin, B. & Roeder, K. Genomic control for association studies. Biometrics 55, 997–1004 (1999).
    Article CAS Google Scholar
25. Zimmermann, K. et al. Sensory neuron sodium channel NaV1.8 is essential for pain at low temperatures. Nature 447, 855–858 (2007).
    Article CAS Google Scholar
26. Rabert, D.K. et al. A tetrodotoxin-resistant voltage-gated sodium channel from human dorsal root ganglia, hPN3/SCN10A. Pain 78, 107–114 (1998).
    Article CAS Google Scholar
27. Remme, C.A., Wilde, A.A. & Bezzina, C.R. Cardiac sodium channel overlap syndromes: different faces of SCN5A mutations. Trends Cardiovasc. Med. 18, 78–87 (2008).
    Article CAS Google Scholar
28. Newton-Cheh, C. et al. Common variants at ten loci influence QT interval duration in the QTGEN Study. Nat. Genet. 41, 399–406 (2009).
    Article CAS Google Scholar
29. Pfeufer, A. et al. Common variants at ten loci modulate the QT interval duration in the QTSCD Study. Nat. Genet. 41, 407–414 (2009).
    Article CAS Google Scholar
30. Jay, P.Y. et al. Function follows form: cardiac conduction system defects in Nkx2-5 mutation. Anat. Rec. A Discov. Mol. Cell. Evol. Biol. 280, 966–972 (2004).
    Article Google Scholar
31. Mesbah, K., Harrelson, Z., Théveniau-Ruissy, M., Papaioannou, V.E. & Kelly, R.G. Tbx3 is required for outflow tract development. Circ. Res. 103, 743–750 (2008).
    Article CAS Google Scholar
32. Moskowitz, I.P. et al. A molecular pathway including Id2, Tbx5, and Nkx2-5 required for cardiac conduction system development. Cell 129, 1365–1376 (2007).
    Article CAS Google Scholar
33. Mori, A.D. et al. Tbx5-dependent rheostatic control of cardiac gene expression and morphogenesis. Dev. Biol. 297, 566–586 (2006).
    Article CAS Google Scholar
34. Postma, A.V. et al. A gain-of-function TBX5 mutation is associated with atypical Holt-Oram syndrome and paroxysmal atrial fibrillation. Circ. Res. 102, 1433–1442 (2008).
    Article CAS Google Scholar
35. Hoogaars, W.M. et al. Tbx3 controls the sinoatrial node gene program and imposes pacemaker function on the atria. Genes Dev. 21, 1098–1112 (2007).
    Article CAS Google Scholar
36. Schinzel, A. Ulnar-mammary syndrome. J. Med. Genet. 24, 778–781 (1987).
    Article CAS Google Scholar
37. Gratton, J.P., Bernatchez, P. & Sessa, W.C. Caveolae and caveolins in the cardiovascular system. Circ. Res. 94, 1408–1417 (2004).
    Article CAS Google Scholar
38. Zhao, Y.Y. et al. Defects in caveolin-1 cause dilated cardiomyopathy and pulmonary hypertension in knockout mice. Proc. Natl. Acad. Sci. USA 99, 11375–11380 (2002).
    Article CAS Google Scholar
39. Smits, P. et al. The transcription factors L-Sox5 and Sox6 are essential for cartilage formation. Dev. Cell 1, 277–290 (2001).
    Article CAS Google Scholar
40. Stankunas, K. et al. Pbx/Meis deficiencies demonstrate multigenetic origins of congenital heart disease. Circ. Res. 103, 702–709 (2008).
    Article CAS Google Scholar
41. Pandur, P., Läsche, M., Eisenberg, L.M. & Kühl, M. Wnt-11 activation of a non-canonical Wnt signalling pathway is required for cardiogenesis. Nature 418, 636–641 (2002).
    Article CAS Google Scholar
42. Su, Z.J. et al. A vascular cell-restricted RhoGAP, p73RhoGAP, is a key regulator of angiogenesis. Proc. Natl. Acad. Sci. USA 101, 12212–12217 (2004).
    Article CAS Google Scholar
43. Pe'er, I., Yelensky, R., Altshuler, D. & Daly, M.J. Estimation of the multiple testing burden for genomewide association studies of nearly all common variants. Genet. Epidemiol. 32, 381–385 (2008).
    Article Google Scholar
44. Willems, J.L. et al. The diagnostic performance of computer programs for the interpretation of electrocardiograms. N. Engl. J. Med. 325, 1767–1773 (1991).
    Article CAS Google Scholar
45. Perz, S., et al. & for the KORA Study Group Does computerized ECG analysis provide sufficiently consistent QT interval estimates for genetic research? in Analysis of Biomedical Signals and Images (eds. Jan, J., Kozumplik, J. & Provaznik, I.) 47–49 (Vutium, Brno, Czech Republic, 2004).
46. Arking, D.E. et al. A common genetic variant in the NOS1 regulator NOS1AP modulates cardiac repolarization. Nat. Genet. 38, 644–651 (2006).
    Article CAS Google Scholar
47. van Bemmel, J.H., Kors, J.A. & van Herpen, G. Methodology of the modular ECG analysis system MEANS. Methods Inf. Med. 29, 346–353 (1990).
    Article CAS Google Scholar
48. Rabbee, N. & Speed, T.P. A genotype calling algorithm for Affymetrix SNP arrays. Bioinformatics 22, 7–12 (2006).
    Article CAS Google Scholar
49. Li, Y., Willer, C., Sanna, S. & Abecasis, G. Genotype imputation. Annu. Rev. Genomics Hum. Genet. 10, 387–406 (2009).
    Article CAS Google Scholar
50. Servin, B. & Stephens, M. Imputation based analysis of association studies: candidate regions and quantitative traits. PLoS Genet. 3, e114 (2007).
    Article Google Scholar
51. Chen, W.M. & Abecasis, G. Family-based association tests for genomewide association scans. Am. J. Hum. Genet. 81, 913–926 (2007).
    Article CAS Google Scholar

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Acknowledgements

We gratefully acknowledge all of the participants in the studies. AGES: US National Institutes of Health (NIH) N01-AG-12100, US National Institute on Aging (NIA) and NIH Intramural Research Programs, Hjartavernd (Icelandic Heart Association), Althingi (Icelandic parliament), US National Heart, Lung, and Blood Institute (NHLBI), US National Eye Institute and US National Institute on Deafness and Other Communication Disorders. ARIC: NHLBI N01-HC-55015, N01-HC-55016, N01-HC-55018 through N01-HC-55022, R01-HL-087641, R01-HL-59367, R01-HL-086694 and R01-HL-054512; US National Human Genome Research Institute (NHGRI) U01-HG004402; NIH HHSN268200625226C; and the Donald W. Reynolds Cardiovascular Clinical Research Center. Infrastructure was supported by NIH UL1-RR025005. CCAF: NHLBI R01-HL090620 and P50-HL077107, and intramural funding from the Heart and Vascular Institute, Department of Cardiovascular Medicine, Cleveland Clinic. CHS: NHLBI N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01-HC-15103, N01-HC-55222, N01-HC-75150, N01-HC-45133, U01-HL-080295, R01-HL-087652 and R01-HL-088456; 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; and the Cedars-Sinai Board of Governors. FHS: NIH N01-HC-25195, HL-076784, AG-028321, N01-HC25195, HL-080025 and 6R01-NS-17950; NHLBI N01-HC-25195; Boston University School of Medicine and Boston Medical Center (LINGA-II); the Robert Dawson Evans Endowment; the Doris Duke Charitable Foundation; the SHARe project; Deutsche Forschungsgemeinschaft fellowship SCHN 1149/1-1; Affymetrix contract for genotyping services (N02-HL-6-4278); and Pfizer. KORA/AFNET: We thank B. Pütz, M. Putz and G. Fischer for their contributions to genotyping and imputation. Bundesministerium für Bildung und Forschung Nationales Genomforschungsnetz; 01-GS-0499, 01-GR-0103, 01-GR-0803, AFNET 01-GI-0204 01-GS-0838, the Leducq Foundation 07-CVD 03, Ludwig-Maximilians University (LMU) FöFoLe 557/569, the LMU Excellence Initiative, MC Health as part of LMUinnovativ, the Helmholtz Zentrum München für Gesundheit und Umwelt and the state of Bavaria. Rotterdam Study: We thank P. Arp, M. Jhamai, M. Moorhouse, M. Verkerk and S. Bervoets for their help in creating the database, K. Estrada for his help with the analyses and M. Struchalin for contributions to genotype imputation. Nederlandse Organisatie voor Wetenschappelijk Onderzoek (The Netherlands Organisation for Scientific Research) 175.010.2005.011, 911.03.012 and 050-060-810, the Research Institute of Diseases in the Elderly, Netherlands Genome Initiative, Stichting Zorgonderzoek Nederland-Medische Wetenschappen (The Netherlands Organisation for Health Research and Development), Netherlands Hartstichting, Netherlands Ministry of Education Culture and Science, Netherlands Ministry of Health Welfare and Sports; the European Commission; Erasmus Medical Center, Erasmus University Rotterdam and the municipality of Rotterdam. SardiNIA: We thank A. Scuteri and M. Orrù for longstanding, continual support of the project and for phenotype characterization. NIA NO1-AG-1-2109, 263-MA-410953, NIH and NIA Intramural Research Programs, NHGRI and NHLBI. Role of the sponsors: None of the funding organizations had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; or preparation, review or approval of the manuscript. More detailed acknowledgments can be found in the Supplementary Note.

Author information

Author notes

1. Arne Pfeufer, Charlotte van Noord, Kristin D Marciante, Dan E Arking, Martin G Larson, Albert Vernon Smith, Kirill V Tarasov, Vilmundur Gudnason, Patrick T Ellinor, Serena Sanna, Stefan Kääb, Jacqueline C M Witteman, Alvaro Alonso, Emelia J Benjamin and Susan R Heckbert: These authors contributed equally to this work.

Authors and Affiliations

1. Institute of Human Genetics, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany
   Arne Pfeufer & Thomas Meitinger
2. Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
   Arne Pfeufer & Thomas Meitinger
3. Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands
   Charlotte van Noord, Germaine C Verwoert, Fernando Rivadeneira, Albert Hofman, Bruno H C Stricker, André G Uitterlinden, Cornelia M van Duijn & Jacqueline C M Witteman
4. Dutch Medicines Evaluation Board, The Hague, The Netherlands
   Charlotte van Noord
5. Netherlands Consortium on Healthy Aging (NCHA) Leiden, The Netherlands
   Charlotte van Noord & Jacqueline C M Witteman
6. Department of Medicine, University of Washington, Seattle, Washington, USA
   Kristin D Marciante, Joshua C Bis & Bruce M Psaty
7. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, Maryland, USA
   Dan E Arking, Georg B Ehret & Aravinda Chakravarti
8. Department of Mathematics and Statistics, Boston University, Boston, Massachusetts, USA
   Martin G Larson
9. National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, USA
   Martin G Larson, Thomas J Wang, Renate B Schnabel, Ramachandran S Vasan, Daniel Levy & Emelia J Benjamin
10. Icelandic Heart Association, Heart Preventive Clinic and Research Institute, Kopavogur, Iceland
    Albert Vernon Smith, Thor Aspelund, Gudny Eiriksdottir & Vilmundur Gudnason
11. Laboratory of Cardiovascular Science, National Institute on Aging, Baltimore, Maryland, USA
    Kirill V Tarasov, Samer S Najjar & Edward Lakatta
12. Laboratory of Genetics, National Institute on Aging, Baltimore, Maryland, USA
    Kirill V Tarasov & David Schlessinger
13. Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
    Martina Müller, Wiebke Sauter, Christian Gieger & H-Erich Wichmann
14. Department of Medicine I, Klinikum Grosshadern, Munich, Germany
    Martina Müller, Moritz F Sinner, Britt M Beckmann & Stefan Kääb
15. Division of Cardiology, Department of Medicine, University of Washington, Seattle, Washington, USA
    Nona Sotoodehnia
16. Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
    Germaine C Verwoert, Fernando Rivadeneira, Bruno H C Stricker & André G Uitterlinden
17. Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland, USA
    Man Li, W H Linda Kao, Anna Köttgen & Josef Coresh
18. Department of Epidemiology, University of Washington, Seattle, Washington, USA
    Bruce M Psaty & Susan R Heckbert
19. Department of Health Services, University of Washington, Seattle, Washington, USA
    Bruce M Psaty
20. Group Health Research Institute, Seattle, Washington, USA
    Bruce M Psaty & Susan R Heckbert
21. Department of Biostatistics, University of Washington, Seattle, Washington, USA
    Kenneth Rice
22. Department of Common Diseases Genetics Program, Medical Genetics Institute, Cedars-Sinai Medical Center, West Hollywood, California, USA
    Jerome I Rotter
23. Department of Medical Informatics, Erasmus Medical Center, Rotterdam, The Netherlands
    Jan A Kors
24. Inspectorate for Health Care, The Hague, The Netherlands
    Bruno H C Stricker
25. Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA
    Steven A Lubitz
26. Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA
    Steven A Lubitz, Christopher Newton-Cheh, Thomas J Wang & Patrick T Ellinor
27. Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA
    Christopher Newton-Cheh & Patrick T Ellinor
28. Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts, USA
    Christopher Newton-Cheh, Thomas J Wang & Patrick T Ellinor
29. Boston University School of Medicine, Boston, Massachusetts, USA
    Jared W Magnani & Ramachandran S Vasan
30. Gutenberg Heart Study, Medical Clinic II (Cardiology), Johannes Gutenberg-University, Mainz, Germany
    Renate B Schnabel
31. Heart & Vascular and Lerner Research Institutes, Cleveland Clinic, Cleveland, Ohio, USA
    Mina K Chung, John Barnard, Jonathan D Smith & David R Van Wagoner
32. Heart Preventive Clinical and Research Institute, University of Iceland, Reykjavik, Iceland
    Thor Aspelund & Vilmundur Gudnason
33. Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, Baltimore, Maryland, USA
    Tamara B Harris & Lenore J Launer
34. Istituto di Neurogenetica e Neurofarmacologia, Consiglio Nazionale delle Ricerche, Monserrato, Cagliari, Italy.,
    Manuela Uda & Serena Sanna
35. Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA
    Gonçalo R Abecasis
36. Statistical Genetics, Max Planck Institute of Psychiatry, Munich, Germany
    Bertram Müller-Myhsok
37. Human Genetics Center and Institute for Molecular Medicine, University of Texas Health Science Center, Houston, Texas, USA
    Eric Boerwinkle
38. Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA
    Aravinda Chakravarti
39. Department of Epidemiology and Prevention, Division of Public Health Sciences, Epidemiological Cardiology Research Center (EPICARE), Wake Forest University Medical Center, Winston-Salem, North Carolina, USA
    Elsayed Z Soliman
40. Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA
    Kathryn L Lunetta
41. Institute of Biological and Medical Imaging, Helmholtz Center, Munich, Germany
    Siegfried Perz
42. Institute of Medical Informatics, Biometry and Epidemiology, Chair of Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany
    H-Erich Wichmann
43. Klinikum Grosshadern, Munich, Germany
    H-Erich Wichmann
44. Center for Population Studies, National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA
    Daniel Levy
45. Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA
    Alvaro Alonso
46. Department of Epidemiology, School of Public Health, Boston University, Boston, Massachusetts, USA
    Emelia J Benjamin
47. Cardiology and Preventive Medicine Division, Evans Department of Medicine, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts, USA
    Emelia J Benjamin

Authors

1. Arne Pfeufer
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2. Charlotte van Noord
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3. Kristin D Marciante
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4. Dan E Arking
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5. Martin G Larson
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6. Albert Vernon Smith
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7. Kirill V Tarasov
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8. Martina Müller
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9. Nona Sotoodehnia
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10. Moritz F Sinner
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11. Germaine C Verwoert
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12. Man Li
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13. W H Linda Kao
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14. Anna Köttgen
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15. Josef Coresh
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16. Joshua C Bis
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17. Bruce M Psaty
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18. Kenneth Rice
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19. Jerome I Rotter
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20. Fernando Rivadeneira
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21. Albert Hofman
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22. Jan A Kors
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23. Bruno H C Stricker
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24. André G Uitterlinden
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25. Cornelia M van Duijn
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26. Britt M Beckmann
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27. Wiebke Sauter
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28. Christian Gieger
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29. Steven A Lubitz
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30. Christopher Newton-Cheh
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31. Thomas J Wang
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32. Jared W Magnani
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33. Renate B Schnabel
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34. Mina K Chung
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35. John Barnard
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36. Jonathan D Smith
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37. David R Van Wagoner
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38. Ramachandran S Vasan
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39. Thor Aspelund
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40. Gudny Eiriksdottir
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41. Tamara B Harris
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42. Lenore J Launer
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43. Samer S Najjar
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44. Edward Lakatta
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45. David Schlessinger
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46. Manuela Uda
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47. Gonçalo R Abecasis
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48. Bertram Müller-Myhsok
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49. Georg B Ehret
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50. Eric Boerwinkle
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51. Aravinda Chakravarti
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52. Elsayed Z Soliman
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53. Kathryn L Lunetta
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54. Siegfried Perz
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55. H-Erich Wichmann
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56. Thomas Meitinger
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57. Daniel Levy
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58. Vilmundur Gudnason
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59. Patrick T Ellinor
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60. Serena Sanna
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61. Stefan Kääb
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62. Jacqueline C M Witteman
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63. Alvaro Alonso
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64. Emelia J Benjamin
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65. Susan R Heckbert
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Study concept and design: A.P., D.E.A., A.V.S., N.S., J.I.R., A.H., B.H.C.S., C.M.v.D., G.E., A.C., K.L.L., V.G., P.T.E., S.S., S.K., J.C.M.W., E.J.B., S.R.H. Acquisition of data: A.P., C.v.N., D.E.A., K.V.T., M.F.S., J.I.R., F.R., J.A.K., B.H.C.S., A.G.U., B.M.B., W.S., C.G., C.N.-C., T.J.W., M.K.C., J.D.S., D.R.V.W., S.S.N., G.B.E., A.C., E.Z.S., S.P., J.C.M.W., A.A., S.R.H. Analysis and interpretation of data: A.P., C.v.N., K.D.M., D.E.A., A.V.S., M.M., N.S., G.C.V., M.L., J.I.R., C.N.-C., T.J.W., R.S.V., T.A., S.S.N., G.B.E., A.C., E.Z.S., K.L.L., S.P., V.G., E.J.B., S.R.H. Drafting the manuscript: A.P., D.E.A., N.S., P.T.E., S.K., E.J.B., S.R.H. Critical revision of the manuscript: C.v.N., K.D.M., M.G.L., A.V.S., K.V.T., M.M., M.F.S., G.C.V., W.H.L.K., A.K., J.C., J.C.B., B.M.P., K.R., J.I.R., F.R., A.H., J.A.K., B.H.C.S., A.G.U., C.M.v.D., B.M.B., C.G., S.A.L., C.N.-C., T.J.W., J.W.M., R.B.S., M.K.C., J.B., J.D.S., D.R.V.W., R.S.V., G.E., L.J.L., T.B.H., E.L., D.S., M.U., G.R.A., B.M.-M., E.B., E.Z.S., K.L.L., H.-E.W., T.M., D.L., V.G., S.S., J.C.M.W., A.A. Statistical analysis: A.P., C.v.N., D.E.A., M.G.L., A.V.S., M.M., G.C.V., M.L., W.H.L.K., J.C.B., K.R., T.A., K.L.L. Obtaining funding: A.P., M.F.S., B.M.P., J.I.R., F.R., A.H., A.G.U., M.K.C., J.D.S., R.S.V., G.E., D.S., M.U., G.R.A., E.B., A.C., H.-E.W., T.M., D.L., V.G., J.C.M.W., S.R.H. Study supervision: J.I.R., F.R., A.H., B.H.C.S., A.G.U., C.M.v.D., G.E., A.C., V.G., J.C.M.W., S.R.H. The following authors had full data access and take responsibility for analysis: A.P., C.v.N., M.M., J.I.R., A.C., K.L.L, S.R.H. Cohort study investigators: a list of investigators by cohort study may be found in the Supplementary Note.

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Correspondence toArne Pfeufer or Susan R Heckbert.

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A.C. is a paid member of the scientific advisory board of Affymetrix, a role that is managed by the Committee on Conflict of Interest of the Johns Hopkins University School of Medicine.

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Pfeufer, A., van Noord, C., Marciante, K. et al. Genome-wide association study of PR interval.Nat Genet 42, 153–159 (2010). https://doi.org/10.1038/ng.517

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• Received: 16 July 2009
• Accepted: 20 November 2009
• Published: 10 January 2010
• Issue Date: February 2010
• DOI: https://doi.org/10.1038/ng.517