Common variants in 22 loci are associated with QRS duration and cardiac ventricular conduction (original) (raw)

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Acknowledgements

Acknowledgments are available in the Supplementary Note.

Author information

Author notes

1. Nona Sotoodehnia, Aaron Isaacs, Paul I W de Bakker, Marcus Dörr, Christopher Newton-Cheh, Ilja M Nolte, Pim van der Harst, Martina Müller, Mark Eijgelsheim, Alvaro Alonso, Andrew A Hicks, Sandosh Padmanabhan, Caroline Hayward, Albert Vernon Smith, Ozren Polasek, Steven Giovannone, Jingyuan Fu, Igor Rudan, Harold Snieder, James F Wilson, Peter P Pramstaller, David S Siscovick, Thomas J Wang, Vilmundur Gudnason, Cornelia M van Duijn, Stephan B Felix, Glenn I Fishman, Yalda Jamshidi, Bruno H Ch Stricker, Nilesh J Samani, Stefan Kääb and Dan E Arking: These authors contributed equally to this work.

Authors and Affiliations

1. Division of Cardiology, Department of Medicine, University of Washington, Seattle, Washington, USA
   Nona Sotoodehnia
2. Department of Medicine, Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, USA
   Nona Sotoodehnia, Kristin D Marciante, Joshua C Bis, Bruce M Psaty, Susan R Heckbert & David S Siscovick
3. Department of Epidemiology, Genetic Epidemiology Unit, Erasmus Medical Center (MC), Rotterdam, The Netherlands
   Aaron Isaacs, Mark P S Sie & Cornelia M van Duijn
4. Centre for Medical Systems Biology, Leiden, The Netherlands
   Aaron Isaacs, Ben A Oostra & Cornelia M van Duijn
5. Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
   Paul I W de Bakker
6. Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA
   Paul I W de Bakker
7. Department of Medical Genetics, University Medical Center, Utrecht, The Netherlands
   Paul I W de Bakker
8. Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands
   Paul I W de Bakker
9. Department of Internal Medicine B, Ernst Moritz Arndt University Greifswald, Greifswald, Germany
   Marcus Dörr & Stephan B Felix
10. Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA
    Christopher Newton-Cheh
11. Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts, USA
    Christopher Newton-Cheh & Thomas J Wang
12. National Heart, Lung, and Blood Institute's (NHLBI) Framingham Heart Study, Framingham, Massachusetts, USA
    Christopher Newton-Cheh, Jared W Magnani, Ying A Wang, L Adrienne Cupples, Daniel Levy, Christopher J O'Donnell & Thomas J Wang
13. Department of Epidemiology, Unit of Genetic Epidemiology and Bioinformatics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
    Ilja M Nolte, Jingyuan Fu, Folkert W Asselbergs, Xiaowen Lu & Harold Snieder
14. Department of Cardiology, University Medical Center Groningen, University of Groningen, The Netherlands
    Pim van der Harst, Irene Mateo Leach, Folkert W Asselbergs, Rudolf A de Boer, Wiek H van Gilst & Dirk J van Veldhuisen
15. Institute of Medical Informatics, Biometry and Epidemiology, Chair of Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany
    Martina Müller & H-Erich Wichmann
16. Department of Medicine I, University Hospital Grosshadern, Ludwig-Maximilians-Universität, Munich, Germany
    Martina Müller, Moritz F Sinner & Stefan Kääb
17. Institute of Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany
    Martina Müller, Norman Klopp & H-Erich Wichmann
18. Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands
    Mark Eijgelsheim, Fernando Rivadeneira, André G Uitterlinden, Jacqueline C M Witteman, Albert Hofman & Bruno H Ch Stricker
19. Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA
    Alvaro Alonso & Aaron R Folsom
20. Institute of Genetic Medicine, European Academy Bozen-Bolzano (EURAC), Bolzano, Italy, affiliated institute of the University of Lübeck, Germany.,
    Andrew A Hicks, Arne Pfeufer, Christian Fuchsberger, Christine Schwienbacher, Claudia Beu Volpato & Peter P Pramstaller
21. Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, University Place, Glasgow, UK
    Sandosh Padmanabhan & Anna F Dominiczak
22. Medical Research Council (MRC) Human Genetics Unit, Institute of Genetics and Molecular Medicine, Edinburgh, UK
    Caroline Hayward & Alan F Wright
23. Icelandic Heart Association, Kopavogur, Iceland
    Albert Vernon Smith, Thor Aspelund & Vilmundur Gudnason
24. University of Iceland, Reykjavik, Iceland
    Albert Vernon Smith, Thor Aspelund & Vilmundur Gudnason
25. Andrija Stampar School of Public Health, Medical School, University of Zagreb, Zagreb, Croatia
    Ozren Polasek
26. Leon H. Charney Division of Cardiology, New York University School of Medicine, New York, New York, USA
    Steven Giovannone, Jiaxiang Qu, Fang-Yu Liu & Glenn I Fishman
27. Department of Genetics, University Medical Center Groningen, University of Groningen, The Netherlands
    Jingyuan Fu, Lude Franke, Rudolf S N Fehrmann, Gerard te Meerman & Cisca Wijmenga
28. Section of Cardiovascular Medicine, Boston University School of Medicine, Boston, Massachusetts, USA
    Jared W Magnani
29. Institute of Human Genetics, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany
    Arne Pfeufer & Thomas Meitinger
30. Institute of Human Genetics, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany
    Arne Pfeufer & Thomas Meitinger
31. Department of Medicine, Center for Lung Biology, University of Washington, Seattle, Washington, USA
    Sina A Gharib
32. Interfaculty Institute for Genetics and Functional Genomics, Ernst Moritz Arndt University Greifswald, Greifswald, Germany
    Alexander Teumer & Uwe Völker
33. Department of Epidemiology and the Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, Maryland, USA
    Man Li & W H Linda Kao
34. Department of Internal Medicine, Erasmus, Rotterdam, MC, The Netherlands
    Fernando Rivadeneira, Karol Estrada, André G Uitterlinden & Bruno H Ch Stricker
35. Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland, USA
    Anna Köttgen
36. Clinical Pharmacology and Barts and the London Genome Centre, William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, London, UK
    Toby Johnson, Patricia B Munroe & Mark J Caulfield
37. Barts and the London National Institute of Health Research Cardiovascular Biomedical Research Unit, London, UK
    Toby Johnson, Patricia B Munroe & Mark J Caulfield
38. Department of Biostatistics, University of Washington, Seattle, Washington, USA
    Kenneth Rice
39. Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA
    Ying A Wang & L Adrienne Cupples
40. Centre for Population Health Sciences, University of Edinburgh, Edinburgh, Scotland
    Sarah H Wild, Harry Campbell, Igor Rudan & James F Wilson
41. Department of Cardiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands
    Folkert W Asselbergs
42. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Aravinda Chakravarti & Dan E Arking
43. Department of Medical Informatics, Erasmus MC, Rotterdam, The Netherlands.,
    Jan A Kors, Gé van Herpen & Bruno H Ch Stricker
44. Institute of Clinical Chemistry and Laboratory Medicine, Ernst Moritz Arndt University Greifswald, Greifswald, Germany
    Astrid Petersmann
45. Laboratory of Epidemiology, Demography and Biometry, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA
    Tamara B Harris & Lenore Launer
46. Epidemiological Cardiology Research Center (EPICARE), Wake Forest University School of Medicine, Winston Salem, North Carolina, USA
    Elsayed Z Soliman
47. Department of Epidemiology, University of Washington, Seattle, Washington, USA
    Bruce M Psaty, Susan R Heckbert & David S Siscovick
48. Department of Health Services, University of Washington, Seattle, Washington, USA
    Bruce M Psaty
49. Group Health Research Institute, Group Health Cooperative, Seattle, Washington, USA
    Bruce M Psaty & Susan R Heckbert
50. Department of Clinical Genetics, Erasmus, Rotterdam, MC, The Netherlands
    Ben A Oostra
51. Institute for Biological and Medical Imaging, Helmholtz Zentrum München-German Research Center for Environmental Health,, Neuherberg, Germany
    Siegfried Perz
52. Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), Rotterdam, The Netherlands
    André G Uitterlinden, Jacqueline C M Witteman, Albert Hofman, Cornelia M van Duijn & Bruno H Ch Stricker
53. Institute for Community Medicine, Ernst Moritz Arndt University Greifswald, Greifswald, Germany
    Henry Völzke
54. Department of Twin Research and Genetic Epidemiology Unit, St. Thomas' Campus, King's College London, St. Thomas' Hospital, London, UK
    Timothy D Spector, Harold Snieder & Yalda Jamshidi
55. Human Genetics Center, University of Texas Health Science Center at Houston, Houston, Texas, USA
    Eric Boerwinkle
56. Institute for Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas, USA
    Eric Boerwinkle
57. Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA
    Jerome I Rotter
58. National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA
    Daniel Levy & Christopher J O'Donnell
59. Klinikum Grosshadern, Munich, Germany
    H-Erich Wichmann
60. Department of Pharmacology, Center for Pharmacology and Experimental Therapeutics, Ernst Moritz Arndt University Greifswald, Greifswald, Germany
    Heyo K Kroemer
61. Department of Experimental and Diagnostic Medicine, University of Ferrara, Ferrara, Italy
    Christine Schwienbacher
62. University of Dundee, Ninewells Hospital and Medical School, Dundee, UK
    John M Connell
63. Blizard Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
    Lude Franke
64. Department of Pulmonology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.,
    Harry J M Groen
65. Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.,
    Rinse K Weersma
66. Department of Neurology, Rudolf Magnus Institute, University Medical Center Utrecht, University of Utrecht, Utrecht, The Netherlands
    Leonard H van den Berg
67. Department of Medical Genetics and Rudolf Magnus Institute, University Medical Center Utrecht, Utrecht, The Netherlands
    Roel A Ophoff
68. Center for Neurobehavioral Genetics, University of California, Los Angeles, California, USA
    Roel A Ophoff
69. Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
    Gerjan Navis
70. Centre for Global Health, Medical School, University of Split, Split, Croatia
    Igor Rudan
71. Gen-info Ltd, Zagreb, Croatia
    Igor Rudan
72. Department of Neurology, General Central Hospital, Bolzano, Italy
    Peter P Pramstaller
73. Department of Neurology, University of Lübeck, Lübeck, Germany
    Peter P Pramstaller
74. Division of Clinical Developmental Sciences, St. George's University of London, London, UK
    Yalda Jamshidi
75. Inspectorate of Health Care, The Hague, The Netherlands
    Bruno H Ch Stricker
76. Department of Cardiovascular Sciences, University of Leicester, Leicester, UK
    Nilesh J Samani
77. Leicester NIHR Biomedical Research Unit in Cardiovascular Disease Glenfield Hospital, Leicester, UK
    Nilesh J Samani

Authors

1. Nona Sotoodehnia
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2. Aaron Isaacs
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3. Paul I W de Bakker
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4. Marcus Dörr
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5. Christopher Newton-Cheh
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6. Ilja M Nolte
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7. Pim van der Harst
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8. Martina Müller
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9. Mark Eijgelsheim
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10. Alvaro Alonso
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11. Andrew A Hicks
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12. Sandosh Padmanabhan
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13. Caroline Hayward
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14. Albert Vernon Smith
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15. Ozren Polasek
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16. Steven Giovannone
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17. Jingyuan Fu
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18. Jared W Magnani
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19. Kristin D Marciante
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20. Arne Pfeufer
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21. Sina A Gharib
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22. Alexander Teumer
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23. Man Li
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24. Joshua C Bis
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25. Fernando Rivadeneira
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26. Thor Aspelund
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27. Anna Köttgen
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28. Toby Johnson
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29. Kenneth Rice
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30. Mark P S Sie
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31. Ying A Wang
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32. Norman Klopp
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33. Christian Fuchsberger
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34. Sarah H Wild
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35. Irene Mateo Leach
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36. Karol Estrada
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37. Uwe Völker
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38. Alan F Wright
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39. Folkert W Asselbergs
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40. Jiaxiang Qu
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41. Aravinda Chakravarti
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42. Moritz F Sinner
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43. Jan A Kors
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44. Astrid Petersmann
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45. Tamara B Harris
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46. Elsayed Z Soliman
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47. Patricia B Munroe
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Contributions

Study concept and design: N.S., A.A., D.E.A., P.I.W.d.B., E.B., H.C., A.C., C.M.v.D., M.E., S.B.F., G.I.F., A.R.F., J.F., V.G., P.v.d.H., S.R.H., A.A.H., A.H., A.I., S.K., H.K.K., C.N.-C., B.A.O., A. Pfeufer, P.P.P., B.M.P., J.I.R., I.R., H.S., E.Z.S., B.H.C.S., A.G.U., A.V.S., U.V., H.V., T.J.W., J.F.W., A.F.W., N.J.S., Y.J.

Acquisition of data: A.A., D.E.A., L.H.v.d.B., R.A.d.B., E.B., M.J.C., A.C., J.M.C., A.F.D., M.D., C.M.v.D., R.S.N.F., A.R.F., L.F., S.G., H.J.M.G., T.B.H., P.v.d.H., C.H., G.v.H., A.I., W.H.L.K., N.K., J.A.K., A.K., L.L., M.L., F.-Y.L., I.M.L., G.t.M., P.B.M., G.N., C.N.-C., B.A.O., R.A.O., S. Perz, A. Pfeufer, A. Petersmann, O.P., B.M.P., J.Q., F.R., J.I.R., I.R., N.J.S., C.S., M.P.S.S., M.F.S., E.Z.S., B.H.C.S., A.T., A.G.U., D.J.v.V., C.B.V., R.K.W., C.W., J.F.W., J.C.M.W., D.L., T.D.S.

Statistical analysis and interpretation of data: A.A., D.E.A., T.A., P.I.W.d.B., N.S., E.B., A.C., L.A.C., M.E., K.E., G.I.F., A.R.F., L.F., J.F., C.F., S.A.G., W.H.v.G., S.G., V.G., P.v.d.H., C.H., S.R.H., A.I., T.J., W.H.L.K., X.L., K.D.M., I.M.L., M.M., I.M.N., S. Padmanabhan, A. Pfeufer, O.P., B.M.P., K.R., H.S., A.T., A.V.S., S.H.W., Y.A.W., N.J.S.

Drafting of the manuscript: N.S., A.A., D.E.A, F.W.A., P.I.W.d.B., M.D., C.M.v.D,. M.E., G.I.F., J.F., S.A.G., V.G., C.H., A.I., Y.J., S.K., J.W.M., I.M.N., O.P., N.J.S., H.S., C.N.-C., P.v.d.H.

Critical revision of the manuscript: A.A., D.E.A., T.A., F.W.A., J.C.B., R.A.d.B., E.B., H.C., M.J.C., A.C., J.M.C., L.A.C., A.F.D., M.D., C.M.v.D., M.E., K.E., S.B.F., G.I.F., A.R.F., J.F., W.H.v.G., V.G., T.B.H., P.v.d.H., C.H., S.R.H., G.v.H., A.A.H., A.H., A.I., Y.J., T.J., S.K., W.H.L.K., N.K., J.A.K., A.K., H.K.K., L.L., D.L., M.L., J.W.M., I.M.L., T.M., M.M., P.B.M., G.N., C.N.-C., I.M.N., C.J.O., B.A.O., S. Padmanabhan, S. Perz, A. Pfeufer, A. Petersmann, O.P., B.M.P., F.R., J.I.R., I.R., M.P.S.S., M.F.S., D.S.S., H.S., B.H.C.S., E.Z.S., A.T., A.G.U., D.J.v.V., U.V., H.V., T.J.W., H.-E.W., A.V.S., S.H.W., J.F.W., J.C.M.W., A.F.W.

Obtained funding: L.H.v.d.B., E.B., H.C., M.J.C., A.C., J.M.C., A.F.D., C.M.v.D., S.B.F., G.I.F., W.H.v.G., H.J.M.G., V.G., P.v.d.H., A.H., Y.J., S.K., H.K.K., L.L., P.B.M., G.N., C.N.-C., C.J.O., B.A.O., R.A.O., P.P.P., B.M.P., J.I.R., I.R., N.J.S., N.S., T.D.S., A.G.U., D.J.v.V., U.V., H.V., T.J.W., R.K.W., H.-E.W., C.W., J.F.W., A.F.W., D.L.

Corresponding authors

Correspondence toNona Sotoodehnia, Stefan Kääb or Dan E Arking.

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Competing interests

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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Sotoodehnia, N., Isaacs, A., de Bakker, P. et al. Common variants in 22 loci are associated with QRS duration and cardiac ventricular conduction.Nat Genet 42, 1068–1076 (2010). https://doi.org/10.1038/ng.716

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• Received: 03 May 2010
• Accepted: 19 October 2010
• Published: 14 November 2010
• Issue Date: December 2010
• DOI: https://doi.org/10.1038/ng.716