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Genetic Loci Associated With Heart Rate Variability and Their Effects on Cardiac Disease Risk Publisher Pubmed



Nolte IM1 ; Munoz ML1 ; Tragante V2 ; Amare AT1, 3, 4 ; Jansen R5 ; Vaez A1, 6 ; Von Der Heyde B7, 8 ; Avery CL9 ; Bis JC10 ; Dierckx B11, 12 ; Van Dongen J13 ; Gogarten SM14 ; Goyette P15 ; Hernesniemi J16, 17, 18 Show All Authors
Authors
  1. Nolte IM1
  2. Munoz ML1
  3. Tragante V2
  4. Amare AT1, 3, 4
  5. Jansen R5
  6. Vaez A1, 6
  7. Von Der Heyde B7, 8
  8. Avery CL9
  9. Bis JC10
  10. Dierckx B11, 12
  11. Van Dongen J13
  12. Gogarten SM14
  13. Goyette P15
  14. Hernesniemi J16, 17, 18
  15. Huikari V19
  16. Hwang SJ20, 21
  17. Jaju D22
  18. Kerr KF14
  19. Kluttig A23
  20. Krijthe BP24
  21. Kumar J7, 8
  22. Van Der Laan SW25
  23. Lyytikainen LP16, 17
  24. Maihofer AX26, 27
  25. Minassian A26, 27
  26. Van Der Most PJ1
  27. Mullernurasyid M28, 29, 30
  28. Nivard M13, 31
  29. Salvi E32
  30. Stewart JD9, 33
  31. Thayer JF34
  32. Verweij N35
  33. Wong A36
  34. Zabaneh D37, 38
  35. Zafarmand MH39, 40
  36. Abdellaoui A13, 31
  37. Albarwani S41
  38. Albert C42
  39. Alonso A43
  40. Ashar F44
  41. Auvinen J45
  42. Axelsson T46
  43. Baker DG26, 27
  44. De Bakker PIW47, 48
  45. Barcella M32
  46. Bayoumi R49
  47. Bieringa RJ1
  48. Boomsma D13, 31
  49. Boucher G15
  50. Britton AR50
  51. Christophersen IE51, 52, 53
  52. Dietrich A54
  53. Ehret GB55, 56
  54. Ellinor PT52, 57
  55. Eskola M18, 58
  56. Felix JF24
  57. Floras JS59, 60
  58. Franco OH24
  59. Friberg P61
  60. Gademan MGJ39
  61. Geyer MA26
  62. Giedraitis V62
  63. Hartman CA63
  64. Hemerich D2, 64
  65. Hofman A24
  66. Hottenga JJ13, 31
  67. Huikuri H65
  68. Hutrikahonen N66, 67
  69. Jouven X68
  70. Junttila J65
  71. Juonala M69, 70
  72. Kiviniemi AM65
  73. Kors JA71
  74. Kumari M50, 72
  75. Kuznetsova T73
  76. Laurie CC14
  77. Lefrandt JD74
  78. Li Y75
  79. Li Y75
  80. Liao D79
  81. Limacher MC80
  82. Lin HJ81, 82
  83. Lindgren CM83, 84
  84. Lubitz SA52, 57
  85. Mahajan A84
  86. Mcknight B10, 14, 85
  87. Meyer Zu Schwabedissen H86
  88. Milaneschi Y5
  89. Mononen N16, 17
  90. Morris AP84, 87
  91. Nalls MA88
  92. Navis G89
  93. Neijts M13, 31
  94. Nikus K18, 90
  95. North KE9, 91
  96. Oconnor DT92
  97. Ormel J63
  98. Perz S93
  99. Peters A30, 93, 94
  100. Psaty BM10, 95, 96
  101. Raitakari OT97, 98
  102. Risbrough VB26, 27
  103. Sinner MF29, 30
  104. Siscovick D99
  105. Smit JH5
  106. Smith NL96, 100, 101
  107. Soliman EZ102
  108. Sotoodehnia N103
  109. Staessen JA73
  110. Stein PK104
  111. Stilp AM14
  112. Stolarzskrzypek K105
  113. Strauch K28, 106
  114. Sundstrom J107
  115. Swenne CA108
  116. Syvanen AC46
  117. Tardif JC15, 109
  118. Taylor KD110
  119. Teumer A111
  120. Thornton TA14
  121. Tinker LE85
  122. Uitterlinden AG24, 112, 113
  123. Van Setten J2
  124. Voss A114
  125. Waldenberger M93, 115
  126. Wilhelmsen KC116, 117
  127. Willemsen G13, 31
  128. Wong Q14
  129. Zhang ZM102, 118
  130. Zonderman AB119
  131. Cusi D120, 121
  132. Evans MK119
  133. Greiser HK122
  134. Van Der Harst P35
  135. Hassan M41
  136. Ingelsson E7, 8, 123
  137. Jarvelin MR19, 45, 124, 125
  138. Kaab S29, 30
  139. Kahonen M126, 127
  140. Kivimaki M50
  141. Kooperberg C85
  142. Kuh D36
  143. Lehtimaki T16, 17
  144. Lind L107
  145. Nievergelt CM26, 27
  146. Odonnell CJ20, 21, 128
  147. Oldehinkel AJ63
  148. Penninx B5
  149. Reiner AP85, 100
  150. Riese H63
  151. Van Roon AM74
  152. Rioux JD15, 109
  153. Rotter JI110
  154. Sofer T14
  155. Stricker BH24, 129
  156. Tiemeier H11, 24
  157. Vrijkotte TGM39
  158. Asselbergs FW2, 130, 131
  159. Brundel BJJM132
  160. Heckbert SR10, 100
  161. Whitsel EA9, 133
  162. Den Hoed M7, 8
  163. Snieder H1
  164. De Geus EJC13, 31
Show Affiliations
Authors Affiliations
  1. 1. Department of Epidemiology, University of Groningen, University Medical Center Groningen, PO Box 30001, Groningen, 9700 RB, Netherlands
  2. 2. Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, 3584CX, Netherlands
  3. 3. Department of Epidemiology, School of Medicine, University of Adelaide, Adelaide, 5005, SA, Australia
  4. 4. College of Medicine and Health Sciences, Bahir Dar University, Bahir Dar, 6000, Ethiopia
  5. 5. Department of Psychiatry, EMGO Institute for Health and Care Research, Neuroscience Campus Amsterdam, VU University Medical Center/GGZ InGeest, Amsterdam, 1081 BT, Netherlands
  6. 6. School of Medicine, Isfahan University of Medical Sciences, Isfahan, 81746-73461, Iran
  7. 7. Department of Medical Sciences, Molecular Epidemiology, Uppsala University, Uppsala, 75237, Sweden
  8. 8. Science for Life Laboratory, Uppsala University, Uppsala, 75237, Sweden
  9. 9. Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, 27599, NC, United States
  10. 10. Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, 98104, WA, United States
  11. 11. Department of Child and Adolescent Psychiatry/Psychology, Department of Child and Adolescent Psychiatry, PO Box 2060, Rotterdam, 3000 CB, Netherlands
  12. 12. ZGeneration R Study Group, Erasmus MC, PO Box 2060, Rotterdam, 3000 CB, Netherlands
  13. 13. Department of Biological Psychology, Behavioral and Movement Sciences, VU University, Amsterdam, 1081 BT, Netherlands
  14. 14. Department of Biostatistics, School of Public Health, University of Washington, Seattle, 98195, WA, United States
  15. 15. Montreal Heart Institute, Montreal, H1T 1C8, QC, Canada
  16. 16. Department of Clinical Chemistry, Fimlab Laboratories, Tampere, 33520, Finland
  17. 17. Department of Clinical Chemistry, University of Tampere School of Medicine, Tampere, 33014, Finland
  18. 18. Department of Cardiology, Heart Hospital, Tampere University Hospital, Tampere, 33521, Finland
  19. 19. Center for Life Course Health Research, University of Oulu, Oulu, 90014, Finland
  20. 20. Framingham Heart Study, Framingham, 01702, MA, United States
  21. 21. Population Sciences Branch, National Heart, Lung and Blood Institute, Bethesda, 20892, MD, United States
  22. 22. Department of Clinical Physiology, Sultan Qaboos University Hospital, Muscat-Al Khoudh, 123, Oman
  23. 23. Institute of Medical Epidemiology, Biostatistics and Informatics, Martin-Luther-University Halle-Wittenberg, Halle (Saale), 06097, Germany
  24. 24. Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, PO Box 2060, Rotterdam, 3000 CB, Netherlands
  25. 25. Laboratory of Experimental Cardiology, Department of Heart and Lung, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, 3584 CX, Netherlands
  26. 26. Department of Psychiatry, University of California, San Diego, San Diego, 92093, CA, United States
  27. 27. Center for Stress and Mental Health (CESAMH), VA San Diego Healthcare System, San Diego, 92161, CA, United States
  28. 28. Institute of Genetic Epidemiology, Helmholtz Zentrum Munchen- German Research Center for Environmental Health, Neuherberg, 85764, Germany
  29. 29. Department of Medicine, University Hospital Munich, Ludwig- Maximilians-University, Munich, 80539, Germany
  30. 30. DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, 80336, Germany
  31. 31. EMGO Institute for Health and Care Research, VU University, VU University Medical Center, Amsterdam, 1081 HV, Netherlands
  32. 32. Department of Health Sciences, University of Milano, Milano, 20122, Italy
  33. 33. Carolina Population Center, University of North Carolina, Chapel Hill, 27599, NC, United States
  34. 34. Department of Psychology, Ohio State University, 1835 Neil Avenue, Columbus, 43210, OH, United States
  35. 35. Department of Cardiology, University of Groningen, University Medical Center Groningen, PO Box 30001, Groningen, 9700 RB, Netherlands
  36. 36. MRC Unit for Lifelong Health and Ageing, University College London, 33 Bedford Place, London, WC1B 5JU, United Kingdom
  37. 37. Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, London, SE5 8AF, United Kingdom
  38. 38. University College London Genetics Institute, University College London, London, WC1E 6BT, United Kingdom
  39. 39. Department of Public Health, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, 1105 AZ, Netherlands
  40. 40. Department of Obstetrics and Gynaecology, Academic Medical Centre, University of Amsterdam, Amsterdam, 1105 AZ, Netherlands
  41. 41. Department of Physiology, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat Al-Khoudh, 123, Oman
  42. 42. Brigham and Women's Hospital, Harvard Medical School, Boston, 02115, MA, United States
  43. 43. Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, 30322, GA, United States
  44. 44. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, 21205, MD, United States
  45. 45. Unit of Primary Health Care, Oulu University Hospital, Oulu, 90220, Finland
  46. 46. Department of Medical Sciences, Molecular Medicine, Uppsala University, Uppsala, 75237, Sweden
  47. 47. Department of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, 3584 CX, Netherlands
  48. 48. Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, 3584 CX, Netherlands
  49. 49. College of Medicine, Mohammed Bin Rashid University, PO Box 505055, Dubai Healthcare City, 66566, United Arab Emirates
  50. 50. Department of Epidemiology and Public Health, University College London, London, WC1E 6BT, United Kingdom
  51. 51. Cardiovascular Research Center, Massachusetts General Hospital, Boston, 02114, MA, United States
  52. 52. Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, 02114, MA, United States
  53. 53. Department of Medical Research, Baerum Hospital, Vestre Viken Hospital Trust, Rud, 1346, Norway
  54. 54. Department of Child and Adolescent Psychiatry, University of Groningen, University Medical Center Groningen, PO Box 30001, Groningen, 9700 RB, Netherlands
  55. 55. Center for Complex Disease Genomics, McKusick- Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, 21205, MD, United States
  56. 56. Cardiology, Department of Specialties of Internal Medicine, Geneva University Hospital, Geneva, 1211, Switzerland
  57. 57. Cardiac Arrhythmia Service, Cardiovascular Research Center, Massachusetts General Hospital, Boston, 02114, MA, United States
  58. 58. Department of Cardiology, University of Tampere School of Medicine, Tampere, 33014, Finland
  59. 59. University Health Network, Mount Sinai Hospital Division of Cardiology, Department of Medicine, University of Toronto, M5S, ON, Canada
  60. 60. Toronto General Research Institute, University Health Network, Toronto, M5G 2C4, ON, Canada
  61. 61. Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, SE-413 45, Sweden
  62. 62. Department of Public Health and Caring Sciences, Molecular Geriatrics, Uppsala University, Uppsala, 75237, Sweden
  63. 63. Interdisciplinary Center Psychopathology and Emotion Regulation, Department of Psychiatry, University of Groningen, University Medical Center Groningen, PO Box 30001, Groningen, 9700 RB, Netherlands
  64. 64. CAPES Foundation, Ministry of Education of Brazil, Brasilia, 70040-020, DF, Brazil
  65. 65. Research Unit of Internal Medicine, Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, 90220, Finland
  66. 66. Department of Pediatrics, Tampere University Hospital, Tampere, 33521, Finland
  67. 67. Department of Pediatrics, University of Tampere School of Medicine, Tampere, 33014, Finland
  68. 68. INSERM U970, Paris Descartes University, Paris, 75006, France
  69. 69. Department of Medicine, University of Turku, Turku, 20520, Finland
  70. 70. Division of Medicine, Turku University Hospital, Turku, 20521, Finland
  71. 71. Department of Medical Informatics, Erasmus Medical Center, Rotterdam, 3015 CE, Netherlands
  72. 72. ISER, Essex University, Colchester, Essex, CO4 3SQ, United Kingdom
  73. 73. Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven, Department of Cardiovascular Sciences, University of Leuven, Leuven, 3000, Belgium
  74. 74. Department of Internal Medicine, Division of Vascular Medicine, University of Groningen, University Medical Center Groningen, PO Box 30001, Groningen, 9700 RB, Netherlands
  75. 75. Division of Genetic Epidemiology, Institute for Medical Biometry and Statistics, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, 79110, Germany
  76. 76. Department of Genetics, University of North Carolina, Chapel Hill, 27599, NC, United States
  77. 77. Department of Biostatistics, University of North Carolina, Chapel Hill, 27599, NC, United States
  78. 78. Department of Computer Science, University of North Carolina, Chapel Hill, 27599, NC, United States
  79. 79. Division of Epidemiology, Department of Public Health Sciences, Penn State University College of Medicine, Hershey, 17033, PA, United States
  80. 80. Division of Cardiovascular Medicine, University of Florida College of Medicine, Gainesville, 32611, FL, United States
  81. 81. Institute for Translational Genomics and Population Sciences, Department of Pediatrics, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, 90502, CA, United States
  82. 82. Division of Medical Genetics, Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, 90502, CA, United States
  83. 83. Li Ka Shing Centre for Health Information and Discovery, Big Data Institute, University of Oxford, Oxford, OX3 7BN, United Kingdom
  84. 84. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, United Kingdom
  85. 85. Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, 98109, WA, United States
  86. 86. Biopharmacy, Department Pharmaceutical Sciences, University of Basel, Basel, CH-4056, Switzerland
  87. 87. Department of Biostatistics, University of Liverpool, Liverpool, L69 3GL, United Kingdom
  88. 88. Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, 20892, MD, United States
  89. 89. Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, PO Box 30001, Groningen, 9700 RB, Netherlands
  90. 90. Department of Cardiology, University of Tampere, School of Medicine, Tampere, 33014, Finland
  91. 91. Carolina Center for Genome Sciences, University of North Carolina, Chapel Hill, 27599, NC, United States
  92. 92. Department of Medicine, University of California, San Diego, San Diego, 92093, CA, United States
  93. 93. Institute of Epidemiology II, Helmholtz Zentrum Munchen-German Research Center for Environmental Health, Neuherberg, 85764, Germany
  94. 94. German Center for Diabetes Research, Neuherberg, 85764, Germany
  95. 95. Departments of Epidemiology and Health Services, University of Washington, Seattle, 98195, WA, United States
  96. 96. Group Health Research Institute, Group Health Cooperative, Seattle, 98101, WA, United States
  97. 97. Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, 20521, Finland
  98. 98. Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, 20520, Finland
  99. 99. New York Academy of Medicine, New York, 10029, NY, United States
  100. 100. Department of Epidemiology, School of Public Health, University of Washington, Seattle, 98195, WA, United States
  101. 101. Seattle Epidemiologic Research and Information Center, Veterans Affairs Office of Research and Development, Seattle, 98108, WA, United States
  102. 102. Epidemiological Cardiology Research Center (EPICARE), Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, 27157, NC, United States
  103. 103. Cardiovascular Health Research Unit, Division of Cardiology, Departments of Medicine and Epidemiology, University of Washington, Seattle, 98101, WA, United States
  104. 104. Heart Rate Variability Lab, Washington University School of Medicine, St Louis, 63108, MO, United States
  105. 105. First Department of Cardiology, Interventional Electrocardiology and Hypertension, Jagiellonian University Medical College, Cracow, 31-008, Poland
  106. 106. Institute of Medical Informatics, Biometry and Epidemiology, Department of Genetic Epidemiology, Ludwig-Maximilians-Universitat, Munich, 81377, Germany
  107. 107. Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, 751 85, Sweden
  108. 108. Department of Cardiology, Leiden University Medical Center, Leiden, 2300 RC, Netherlands
  109. 109. Universite de Montreal, Montreal, QC, Canada
  110. 110. Institute for Translational Genomics and Population Sciences, Departments of Pediatrics and Medicine, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, 90509, CA, United States
  111. 111. Institute for Community Medicine, University Medicine Greifswald, Greifswald, 17475, Germany
  112. 112. Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, 3015 CE, Netherlands
  113. 113. Netherlands Genomics Initiative (NGI)- Sponsored Netherlands Consortium for Healthy Aging NCHA), Leiden, 2300 RC, Netherlands
  114. 114. Institute of Innovative Health Technologies-IGHT, Jena Ernst-Abbe-Hochschule Jena, Jena, 07745, Germany
  115. 115. Research Unit of Molecular Epidemiology, Helmholtz Zentrum Munchen-German Research Center for Environmental Health, Neuherberg, 85764, Germany
  116. 116. Departments of Genetics and Neurology, University of North Carolina, Chapel Hill, 27599, NC, United States
  117. 117. Renaissance Computing Institute, Chapel Hill, 27599, NC, United States
  118. 118. Department of Epidemiology and Prevention, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, 27157, NC, United States
  119. 119. Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, 21224, MD, United States
  120. 120. Institute of Biomedical Technologies, CNR-Italian National Research Council, Milan, 20090, Italy
  121. 121. KOS Genetic SRL, Bresso (Milano), 20091, Italy
  122. 122. German Cancer Research Centre, Division of Cancer Epidemiology, Heidelberg, 69210, Germany
  123. 123. Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, 94305, CA, United States
  124. 124. Department of Epidemiology and Biostatistics, School of Public Health, Faculty of Medicine, St Mary's Campus, Imperial College London, London, W2 1PG, United Kingdom
  125. 125. Biocenter Oulu, University of Oulu, Oulu, 90014, Finland
  126. 126. Department of Clinical Physiology, Tampere University Hospital, Tampere, 33521, Finland
  127. 127. Department of Clinical Physiology, University of Tampere, School of Medicine, Tampere, 33014, Finland
  128. 128. Cardiology Section, Boston Veteran's Administration Healthcare, Boston, 02132, MD, United States
  129. 129. Inspectorate for Health Care, Hague, 2511 VX, Netherlands
  130. 130. Institute of Cardiovascular Science, University College London, 222 Euston Road, London, NW1 2DA, United Kingdom
  131. 131. Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, 3501 DG, Netherlands
  132. 132. Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, De Boelelaan 1118, Amsterdam, 1081 HV, Netherlands
  133. 133. Department of Medicine, University of North Carolina, Chapel Hill, 27599, NC, United States

Source: Nature Communications Published:2017


Abstract

Reduced cardiac vagal control reflected in low heart rate variability (HRV) is associated with greater risks for cardiac morbidity and mortality. In two-stage meta-analyses of genome-wide association studies for three HRV traits in up to 53,174 individuals of European ancestry, we detect 17 genome-wide significant SNPs in eight loci. HRV SNPs tag non-synonymous SNPs (in NDUFA11 and KIAA1755), expression quantitative trait loci (eQTLs) (influencing GNG11, RGS6 and NEO1), or are located in genes preferentially expressed in the sinoatrial node (GNG11, RGS6 and HCN4). Genetic risk scores account for 0.9 to 2.6% of the HRV variance. Significant genetic correlation is found for HRV with heart rate (-0.74
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