Genetic Determinants of Electrocardiographic P-Wave Duration and Relation to Atrial Fibrillation-Reference-Cited by-同舟云学术

Genetic Determinants of Electrocardiographic P-Wave Duration and Relation to Atrial Fibrillation

Published:2020-10 Issue:5 Volume:13 Page:387-395
ISSN:2574-8300
Container-title:Circulation: Genomic and Precision Medicine
language:en
Short-container-title:Circ: Genomic and Precision Medicine

Author:

Weng Lu-Chen¹²^ORCID,Hall Amelia Weber¹²^ORCID,Choi Seung Hoan²,Jurgens Sean J.²^ORCID,Haessler Jeffrey³,Bihlmeyer Nathan A.⁴^ORCID,Grarup Niels⁵^ORCID,Lin Honghuang⁶⁷^ORCID,Teumer Alexander⁸⁹^ORCID,Li-Gao Ruifang¹⁰^ORCID,Yao Jie¹¹^ORCID,Guo Xiuqing¹¹¹²^ORCID,Brody Jennifer A.¹³^ORCID,Müller-Nurasyid Martina¹⁴¹⁵¹⁶^ORCID,Schramm Katharina¹⁴¹⁵¹⁶,Verweij Niek¹⁷¹⁸,van den Berg Marten E.¹⁹,van Setten Jessica²⁰,Isaacs Aaron²¹²²^ORCID,Ramírez Julia²³²⁴^ORCID,Warren Helen R.²³²⁴^ORCID,Padmanabhan Sandosh²⁵^ORCID,Kors Jan A.²⁶,de Boer Rudolf A.¹⁸^ORCID,van der Meer Peter¹⁸^ORCID,Sinner Moritz F.¹⁵²⁷,Waldenberger Melanie²⁷²⁸²⁹^ORCID,Psaty Bruce M.³⁰³¹^ORCID,Taylor Kent D.¹¹¹²,Völker Uwe⁸³²^ORCID,Kanters Jørgen K.³³^ORCID,Li Man³⁴^ORCID,Alonso Alvaro³⁵^ORCID,Perez Marco V.³⁶^ORCID,Vaartjes Ilonca³⁷,Bots Michiel L.³⁷,Huang Paul L.¹,Heckbert Susan R.³⁸^ORCID,Lin Henry J.¹¹¹²,Kornej Jelena⁶^ORCID,Munroe Patricia B.²³²⁴,van Duijn Cornelia M.³⁹⁴⁰^ORCID,Asselbergs Folkert W.²⁰⁴¹⁴²^ORCID,Stricker Bruno H.⁴³⁴⁴⁴⁵,van der Harst Pim¹⁸⁴⁶⁴⁷^ORCID,Kääb Stefan¹⁵²⁷^ORCID,Peters Annette²⁷²⁸⁴⁸^ORCID,Sotoodehnia Nona¹³,Rotter Jerome I.¹¹⁴⁹^ORCID,Mook-Kanamori Dennis O.¹⁰⁵⁰,Dörr Marcus⁸⁵¹^ORCID,Felix Stephan B.⁸⁵¹,Linneberg Allan⁵²⁵³,Hansen Torben⁵,Arking Dan E.⁴^ORCID,Kooperberg Charles³^ORCID,Benjamin Emelia J.⁶⁵⁴⁵⁵^ORCID,Lunetta Kathryn L.⁶⁵⁶^ORCID,Ellinor Patrick T.¹⁵⁷²^ORCID,Lubitz Steven A.⁵⁷²^ORCID

Affiliation:

1. Cardiovascular Research Center (L.-C.W., A.W.H., P.L.H., P.T.E.), MGH, Boston.

2. Cardiovascular Disease Initiative, The Broad Institute of MIT and Harvard, Cambridge, MA (L.-C.W., A.W.H., S.H.C., S.J.J., P.T.E., S.A.L.).

3. Fred Hutchinson Cancer Research Center, Division of Public Health Sciences, Seattle, WA (J.H., C.K.).

4. McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (N.A.B., D.E.A.).

5. Novo Nordisk Foundation Center for Basic Metabolic Research (N.G., T.H.), Faculty of Health & Medicine Sciences, University of Copenhagen, Denmark.

6. Boston University & NHLBI’s Framingham Heart Study, Framingham, MA (H.L., J.K., E.J.B., K.L.L.).

7. Section of Computational Biomedicine, Department of Medicine (H.L.), Boston University School of Medicine, Boston, MA.

8. DZHK (German Center for Cardiovascular Research), partner site Greifswald, Germany (A.T., U.V., M.D., S.B.F.).

9. Institute for Community Medicine (A.T.), University Medicine Greifswald, Germany.

10. Department of Clinical Epidemiology (R.L.-G., D.O.M.-K.), Leiden University Medical Center, the Netherlands.

11. The Institute for Translational Genomics & Population Sciences at Harbor-UCLA Medical Center, Torrance, CA (J.Y., X.G., K.D.T., H.J.L., J.I.R.).

12. Department of Pediatrics (X.G., K.D.T., H.J.L.), David Geffen School of Medicine at UCLA, Los Angeles, CA.

13. Cardiovascular Health Research Unit, Department of Medicine (J.A.B., N.S.), University of Washington.

14. Chair of Genetic Epidemiology, IBE, Faculty of Medicine, LMU Munich, Germany (M.M.-N., K.S.).

15. Department of Internal Medicine I (Cardiology), Hospital of the Ludwig-Maximilians-University (LMU) Munich, Germany (M.M.-N., K.S., M.F.S., S.K.).

16. Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany (M.M.-N., K.S.).

17. Genomics plc, Oxford, United Kingdom (N.V.).

18. Department of Cardiology (N.V., R.A.d.B., P.v.d.M., P.v.d.H.), University of Groningen & University Medical Center.

19. Department of Epidemiology (M.E.v.d.B.)

20. Erasmus MC, Medical Center Rotterdam, Division of Heart & Lungs, Department of Cardiology, University of Utrecht, University Medical Center Utrecht (J.v.S., F.W.A.).

21. CARIM School for Cardiovascular Diseases (A.I.), Maastricht University, the Netherlands.

22. Department of Physiology (A.I.), Maastricht University, the Netherlands.

23. National Institute for Health Research, Barts Cardiovascular Biomedical Research Center (J.R., H.R.W., P.B.M.), Queen Mary University of London, London.

24. William Harvey Research Institute, Barts & The London School of Medicine & Dentistry (J.R., H.R.W., P.B.M.), Queen Mary University of London, London.

25. Institute of Cardiovascular & Medical Sciences, College of Medical, Veterinary & Life Sciences, University of Glasgow, United Kingdom (S.P.).

26. Department of Medicine Informatics (J.A.K.), Erasmus University Medical Center, Rotterdam, the Netherlands.

27. DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance (M.F.S., M.W., S.K., A.P.).

28. Institute of Epidemiology (M.W., A.P.), Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.

29. Research Unit of Molecular Epidemiology (M.W.), Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.

30. Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology & Health Services (B.M.P.), University of Washington.

31. Kaiser Permanente Washington Health Research Institute, Seattle, WA (B.M.P.).

32. Interfaculty Institute for Genetics & Functional Genomics (U.V.), University Medicine Greifswald, Germany.

33. Lab of Experimental Cardiology (J.K.K.), Faculty of Health & Medicine Sciences, University of Copenhagen, Denmark.

34. Division of Nephrology & Hypertension, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT (M.L.).

35. Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA (A.A.).

36. Department of Medicine, Stanford University, Palo Alto, CA (M.V.P.).

37. Julius Center for Health Sciences & Primary Care, University Medical Center Utrecht, Utrecht University, the Netherlands (I.V., M.L.B.).

38. Cardiovascular Health Research Unit, Department of Epidemiology (S.R.H.), University of Washington.

39. Department of Epidemiology (C.M.v.D.), Erasmus University Medical Center, Rotterdam, the Netherlands.

40. Nuffield Department of Population Health, Medical Sciences Division, St. Cross College, Oxford University (C.M.v.D.).

41. Health Data Research UK & Institute of Health Informatics (F.W.A.), University College London, United Kingdom.

42. Institute of Cardiovascular Science, Faculty of Population Health Sciences (F.W.A.), University College London, United Kingdom.

43. Department of Internal Medicine (B.H.S.)

44. Department of Medicine Informatics (B.H.S.)

45. Inspectorate of Health Care (B.H.S.), ICIN-Netherlands Heart Institute, Utrecht.

46. Department of Genetics (P.v.d.H.), University of Groningen & University Medical Center.

47. Durrer Center for Cardiogenetic Research (P.v.d.H.), ICIN-Netherlands Heart Institute, Utrecht.

48. German Center for Diabetes Research, Neuherberg, Germany (A.P.).

49. Departments of Pediatrics & Human Genetics (J.I.R.), David Geffen School of Medicine at UCLA, Los Angeles, CA.

50. Department of Public Health & Primary Care (D.O.M.-K.), Leiden University Medical Center, the Netherlands.

51. Department of Internal Medicine B (M.D., S.B.F.), University Medicine Greifswald, Germany.

52. Department of Clinical Medicine (A.L.), Faculty of Health & Medicine Sciences, University of Copenhagen, Denmark.

53. Center for Clinical Research & Prevention, Bispebjerg & Frederiksberg Hospital, Copenhagen, Denmark (A.L.).

54. Department of Medicine (E.J.B.), Boston University School of Medicine, Boston, MA.

55. Department of Epidemiology (E.J.B.), Boston University School of Public Health, Boston, MA.

56. Department of Biostatistics (K.L.L.), Boston University School of Public Health, Boston, MA.

57. Cardiac Arrhythmia Service (P.T.E, S.A.L.), MGH, Boston.

Abstract

Background: The P-wave duration (PWD) is an electrocardiographic measurement that represents cardiac conduction in the atria. Shortened or prolonged PWD is associated with atrial fibrillation (AF). We used exome-chip data to examine the associations between common and rare variants with PWD. Methods: Fifteen studies comprising 64 440 individuals (56 943 European, 5681 African, 1186 Hispanic, 630 Asian) and ≈230 000 variants were used to examine associations with maximum PWD across the 12-lead ECG. Meta-analyses summarized association results for common variants; gene-based burden and sequence kernel association tests examined low-frequency variant-PWD associations. Additionally, we examined the associations between PWD loci and AF using previous AF genome-wide association studies. Results: We identified 21 common and low-frequency genetic loci (14 novel) associated with maximum PWD, including several AF loci ( TTN , CAND2 , SCN10A , PITX2 , CAV1 , SYNPO2L , SOX5 , TBX5, MYH6, RPL3L ). The top variants at known sarcomere genes ( TTN, MYH6 ) were associated with longer PWD and increased AF risk. However, top variants at other loci (eg, PITX2 and SCN10A ) were associated with longer PWD but lower AF risk. Conclusions: Our results highlight multiple novel genetic loci associated with PWD, and underscore the shared mechanisms of atrial conduction and AF. Prolonged PWD may be an endophenotype for several different genetic mechanisms of AF.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

General Medicine

Reference46 articles.

1. P Wave Indices

2. P-wave indices and atrial fibrillation: Cross-cohort assessments from the Framingham Heart Study (FHS) and Atherosclerosis Risk in Communities (ARIC) study

3. Genetics of atrial fibrillation: from families to genomes

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