Article open access publication

Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation

Nature Genetics, Springer Nature, ISSN 1061-4036

Volume 47, 11, 2015

DOI:10.1038/ng.3405, Dimensions: pub.1012851637, PMC: PMC4719169, PMID: 26390057,

Authors

Loh, Marie (2) (3) (4)
Wang, Xu (6) (7)
Zhang, Weihua (3) (8)
Saleheen, Danish (10) (11) (12)
Wahl, Simone (14) (15) (16)
Tan, Sian-Tsung (3) (8)
Afzal, Uzma (3) (8)
Ahluwalia, Tarunveer S (17) (18) (19)
Chen, Peng (6) (7)
Esko, Tõnu (22) (23) (24) (25)
Harris, Sarah E (27) (28)
Khor, Chiea Chuen (6) (7) (31)
Wu, Ying (40)
Wu, Jer-Yuarn (41) (42)
Zhang, Yi (43) (44)
Aits, Imke (45)
Postmus, Iris (52) (53)
Raitakari, Olli T (54) (55)
Traglia, Michela (59) (60)
White, Jon (61)
Aung, Tin (66)
Barroso, Inês (48) (67) (68)
Cai, Hui (21) (70)
Chen, Chien-Hsiun (41) (42)
Cheng, Ching-Y U (6) (7) (66) (71)
Chong, Yap-Seng (6) (39)
Courtney, Regina (21) (70)
Do, Loi D (50)
Grewal, Jagvir (3) (8)
He, Jing (21)
Hsu, Chris (29)
Huang, Wei (78)
Koh, Woon-Puay (6) (7) (71)
Lee, Jeannette (6) (7)
Liao, Jiemin (6) (66)
Meitinger, Thomas (86) (87)
Müller-Nurasyid, Martina (88) (89) (90)
Nakashima, Eitaro (92) (93)
Peng, Hao (63)
Peters, Annette (15) (90)
Rahman, Mahfuzar (65) (97)
Tong, Lin (56)
Turjanmaa, Väinö (49) (101)
van Dam, Rob M (6) (7)
Viikari, Jorma S (54) (55)
Wilson, Rory (15) (16)
Wong, Tien Yin (6) (66)
Young, Terri L (71) (104)
Zhou, Xueya (106) (107)
Asselbergs, Folkert W (58) (61) (108)
Deloukas, Panos (109) (110)
Franks, Paul W (24) (47) (98)
Jarvelin, Marjo-Riitta (3) (4) (75)
Jukema, J Wouter (53) (108) (112)
Kähönen, Mika (49) (101)
Lee, Jong-Young (113) (114)
Linneberg, Allan (19) (79)
Samani, Nilesh J (115) (116)
Sørensen, Thorkild I A (19) (96) (117)
Toniolo, Daniela (60) (118)
Danesh, John (11) (68)
Liu, Jianjun (6) (7) (31)
März, Winfried (32) (119) (120)
Shu, Xiao Ou- (21) (70)
Vithana, Eranga (6) (66) (71)
Zheng, Wei (21) (70)
Zhu, Dingliang (43) (44)
McCarthy, Mark I (13) (123)
Gieger, Christian (15) (16)
Teo, Yik-Ying (6) (7) (31) (66)
He, Jiang * (9)
Tai, E Shyong * (6) (7) (82)
van der Harst, Pim * (5) (108)
Kooner, Jaspal S * (3) (8) (124)
Chambers, John C * (3) (8) (124)

* Corresponding author

Affiliations

Organisations

  1. (1) National Center For Global Health and Medicine, grid.45203.30
  2. (2) Agency for Science, Technology and Research, grid.185448.4
  3. (3) Imperial College London, grid.7445.2
  4. (4) University of Oulu, grid.10858.34
  5. (5) University Medical Center Groningen, grid.4494.d
  6. (6) National University of Singapore, grid.4280.e
  7. (7) National University Health System, grid.410759.e
  8. (8) Ealing Hospital, grid.415918.0
  9. (9) Tulane University, grid.265219.b
  10. (10) University of Pennsylvania, grid.25879.31
  11. (11) University of Cambridge, grid.5335.0
  12. (12) Center for Non-Communicable Diseases, grid.497620.e
  13. (13) Wellcome Centre for Human Genetics, grid.270683.8
  14. (14) German Center for Diabetes Research, grid.452622.5
  15. (15) Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany
  16. (16) Research Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany
  17. (17) Copenhagen Prospective Studies on Asthma in Childhood (COSPAC), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
  18. (18) Steno Diabetes Center, grid.419658.7, Capital Region
  19. (19) University of Copenhagen, grid.5254.6, KU
  20. (20) Erasmus University Medical Center, grid.5645.2
  21. (21) Vanderbilt University, grid.152326.1
  22. (22) Boston Children's Hospital, grid.2515.3
  23. (23) Broad Institute, grid.66859.34
  24. (24) Harvard University, grid.38142.3c
  25. (25) University of Tartu, grid.10939.32
  26. (26) Korea National Institute of Health, grid.415482.e
  27. (27) Western General Hospital, grid.417068.c
  28. (28) University of Edinburgh, grid.4305.2
  29. (29) University of Southern California, grid.42505.36
  30. (30) University of Kelaniya, grid.45202.31
  31. (31) Genome Institute of Singapore, grid.418377.e
  32. (32) Heidelberg University, grid.7700.0
  33. (33) Shanghai Institutes for Biological Sciences, grid.419092.7
  34. (34) Nagoya University Hospital, grid.437848.4
  35. (35) Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
  36. (36) Ruddy Canadian Cardiovascular Genetics Centre, Ottawa, Ontario, Canada
  37. (37) University of Ottawa, grid.28046.38
  38. (38) Kyoto University, grid.258799.8
  39. (39) Singapore Institute for Clinical Sciences, grid.452264.3
  40. (40) University of North Carolina at Chapel Hill, grid.10698.36
  41. (41) Institute of Biomedical Sciences, Academia Sinica, grid.482251.8
  42. (42) China Medical University, grid.254145.3
  43. (43) Shanghai Institute of Hypertension, grid.11444.34
  44. (44) Shanghai Jiao Tong University, grid.16821.3c
  45. (45) Kiel University, grid.9764.c
  46. (46) University of Oxford, grid.4991.5
  47. (47) Skåne University Hospital, grid.411843.b
  48. (48) Institute of Metabolic Science, grid.470900.a
  49. (49) Tampere University, grid.502801.e
  50. (50) Bạch Mai Hospital, grid.414163.5
  51. (51) University of Minnesota, grid.17635.36
  52. (52) Netherlands Consortium for Healthy Ageing, grid.452197.c
  53. (53) Leiden University Medical Center, grid.10419.3d
  54. (54) Turku University Hospital, grid.410552.7
  55. (55) University of Turku, grid.1374.1
  56. (56) Department of Public Health Sciences, University of Chicago, Chicago, Illinois, USA
  57. (57) National Research Council, grid.5326.2
  58. (58) University Medical Center Utrecht, grid.7692.a
  59. (59) IRCCS Materno Infantile Burlo Garofolo, grid.418712.9
  60. (60) San Raffaele Hospital, grid.18887.3e
  61. (61) University College London, grid.83440.3b
  62. (62) Kyushu University, grid.177174.3
  63. (63) Soochow University, grid.263761.7
  64. (64) University of North Carolina System, grid.410711.2
  65. (65) University of Chicago Research Bangladesh, grid.452875.9
  66. (66) Singapore National Eye Center, grid.419272.b
  67. (67) National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK
  68. (68) Wellcome Sanger Institute, grid.10306.34
  69. (69) University of Oklahoma Health Sciences Center, grid.266902.9
  70. (70) Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee, USA
  71. (71) Duke NUS Graduate Medical School, grid.428397.3
  72. (72) Shanghai Cancer Institute, grid.419087.3
  73. (73) Chinese Academy of Medical Sciences & Peking Union Medical College, grid.506261.6
  74. (74) Dayanand Medical College & Hospital, grid.413495.e
  75. (75) Oulu University Hospital, grid.412326.0
  76. (76) Cleveland Clinic, grid.239578.2
  77. (77) The University of Texas Health Science Center at Houston, grid.267308.8
  78. (78) Department of Genetics, Chinese National Human Genomic Center, Shanghai, China
  79. (79) Rigshospitalet, grid.475435.4, Capital Region
  80. (80) Mie University, grid.260026.0
  81. (81) Ehime University, grid.255464.4
  82. (82) Osaka University, grid.136593.b
  83. (83) KK Women's and Children's Hospital, grid.414963.d
  84. (84) University of San Carlos, grid.267101.3
  85. (85) Aichi Gakuin University, grid.411253.0
  86. (86) Institute of Human Genetics, Helmholtz Zentrum München–German Research Center for Environmental Health, Neuherberg, Germany
  87. (87) Technical University of Munich, grid.6936.a
  88. (88) Institute of Genetic Epidemiology, Helmholtz Zentrum München–German Research Center for Environmental Health, Neuherberg, Germany
  89. (89) Ludwig Maximilian University of Munich, grid.5252.0
  90. (90) German Centre for Cardiovascular Research, grid.452396.f
  91. (91) Shimane University, grid.411621.1
  92. (92) Chubu Rosai Hospital, grid.410815.9
  93. (93) Nagoya University, grid.27476.30
  94. (94) Department of Cardiology, Heart Centre, Tampere University Hospital and University of Tampere School of Medicine, Tampere, Finland
  95. (95) Teikyo University, grid.264706.1
  96. (96) University of Bristol, grid.5337.2
  97. (97) BRAC, grid.501438.b
  98. (98) Umeå University, grid.12650.30
  99. (99) University of Glasgow, grid.8756.c
  100. (100) Institute for Adult Diseases Asahi Life Foundation, grid.418597.6
  101. (101) Tampere University Hospital, grid.412330.7
  102. (102) Shiga University of Medical Science, grid.410827.8
  103. (103) Yokohama City University, grid.268441.d
  104. (104) Duke University, grid.26009.3d
  105. (105) University of Pittsburgh Cancer Institute, grid.478063.e
  106. (106) Tsinghua University, grid.12527.33
  107. (107) University of Hong Kong, grid.194645.b
  108. (108) Durrer Center for Cardiogenetic Research, Interuniversity Cardiology Institute of the Netherlands (ICIN)–Netherlands Heart Institute, Utrecht, the Netherlands
  109. (109) King Abdulaziz University, grid.412125.1
  110. (110) Queen Mary University of London, grid.4868.2
  111. (111) Hebrew University of Jerusalem, grid.9619.7
  112. (112) ICIN, Utrecht, the Netherlands
  113. (113) Ministry of Health and Welfare, grid.452940.e
  114. (114) THERAGEN ETEX Bio Institute, Suwon, Republic of Korea
  115. (115) Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, UK
  116. (116) Glenfield Hospital, grid.412925.9
  117. (117) Institute of Preventive Medicine, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark
  118. (118) Istituto di Genetica Molecolare, grid.419479.6
  119. (119) Medical University of Graz, grid.11598.34
  120. (120) Synlab (Germany), grid.461810.a
  121. (121) National Hellenic Research Foundation, grid.22459.38
  122. (122) Maastricht University, grid.5012.6
  123. (123) Oxford Centre for Diabetes, Endocrinology and Metabolism, grid.470392.b
  124. (124) Imperial College Healthcare NHS Trust, grid.417895.6

Description

We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10(-11) to 5.0 × 10(-21)). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10(-6)). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.

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University of Copenhagen

Danish Open Access Indicator

2015: Unused

Research area: Medicine

Danish Bibliometrics Indicator

2015: Level 2

Research area: Medicine

Dimensions Citation Indicators

Times Cited: 179

Field Citation Ratio (FCR): 24.11

Relative Citation ratio (RCR): 8.44

Open Access Info

Green, Accepted