Article open access publication

The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals

Nature Genetics, Springer Nature, ISSN 1061-4036

Volume 48, 10, 2016

DOI:10.1038/ng.3667, Dimensions: pub.1007132667, PMC: PMC5042863, PMID: 27618452,

Authors

Ehret, Georg B (1) (2)
Johnson, Toby (7) (8)
Shungin, Dmitry (15) (16)
Kristiansson, Kati (22) (23)
Fava, Cristiano (16) (28)
Pers, Tune H (34) (35) (36) (37)
Zhao, Wei (42)
Wu, Ying (43)
Barroso, Inês (10) (52) (53)
Chambers, John C (19) (61) (62)
Cheng, Ching-Y U (64) (65) (66) (67)
Döring, Angela (12) (69)
Danesh, John (53) (71)
Drenos, Fotios (24) (73)
Erdmann, Jeanette (75) (76)
Esko, Tonu (36) (37)
Fall, Tove (29)
Farrall, Martin (3) (78)
Fraser, Ross M (81) (82)
Gao, He (19)
Gertow, Karl (13) (14)
Goel, Anuj (3) (78)
Goodall, Alison H (85) (86)
Gorski, Mathias (88) (89)
Herzig, Karl-Heinz (92) (97)
Hirschhorn, Joel N (5) (36) (37)
Hofman, Albert (5) (47)
Hunt, Steven C (101) (102)
Illig, Thomas (12) (103)
Kähönen, Mika (27) (105)
Kathiresan, Sekar (5) (36) (106)
Kim, Eric (26)
Klopp, Norman (12) (103)
Kooner, Jaspal S (19) (61) (62)
Kosova, Gulum (36) (106)
Kuh, Diana (108)
Kutalik, Zoltan (60) (109)
Kuusisto, Johanna (110) (111)
Lakka, Timo A (94) (110) (112)
Lee, Nanette R (113) (114)
Lee, I-Te (115) (116)
Liang, Kae-Woei (115) (116)
Lin, Hong Huang (38) (117)
Lin, Li (2)
Lobbens, Stéphane (118) (119) (120)
Müller-Nurasyid, Martina (12) (121) (122)
Marouli, Eirini (8) (123)
McCarthy, Mark I (3) (78)
Moilanen, Leena (93) (110)
Nikus, Kjell (27) (105)
Ong, Ken K (10)
Palmer, Cameron D (36) (37)
Penninx, Brenda W (30) (129) (130)
Perola, Markus (22) (23) (126)
Pramstaller, Peter P (76) (98) (131)
Psaty, Bruce M (55) (132)
Rayner, N William (3) (53) (78)
Renström, Frida (15) (16)
Roberts, Robert (136) (137)
Samani, Nilesh J (85) (86)
Schunkert, Heribert (139) (140) (141) (142)
Sebert, Sylvain (92) (110)
Sheu, Wayne H-H (115) (116) (143)
Sim, Xue Ling (6) (64) (65)
Smith, Albert V (90) (91)
Stančáková, Alena (110) (112)
Tai, E Shyong (64) (65) (66)
Tremoli, Elena (48) (49)
Uusitupa, Matti (110) (112)
Vaez, Ahmad (30) (146)
van Iperen, Erik P A (148) (149)
Voight, Benjamin F (36) (42)
Watkins, Hugh (3) (78)
Wilson, James F (82) (95)
Wong, Tien Y (64) (65) (66) (67)
Yang, Tsun-Po (8) (71)
Yao, Jie (26)
Yengo, Loic (118) (119) (120)
Zhang, Weihua (19) (62)
Bovet, Pascal (45) (154)
Saleheen, Danish (42) (134)
Gierman, Hinco J (39) (155)
Wong, Andrew (108)
Lind, Lars (29)
Schwarz, Peter E H (59) (156)
Laakso, Markku (110) (111)
Rauramaa, Rainer (94) (110)
Tuomilehto, Jaakko (22) (158) (159) (160)
Ingelsson, Erik (29) (31)
März, Winfried (162) (163)
Froguel, Philippe (91) (118) (119) (120)
Jarvelin, Marjo-Riitta (19) (92) (93)
Franks, Paul W (5) (15) (16)
Hamsten, Anders (13) (14)
Wichmann, H-Erich (69) (122) (142)
Stefansson, Kari (9) (90)
Ridker, Paul M (4) (5)
Loos, Ruth J F (10) (164)
Deloukas, Panos (8) (160)
Morris, Andrew P (3) (165)
Newton-Cheh, Christopher * (27) (36) (106)

* Corresponding author

Affiliations

Organisations

  1. (1) Johns Hopkins University, grid.21107.35
  2. (2) University Hospital of Geneva, grid.150338.c
  3. (3) Wellcome Centre for Human Genetics, grid.270683.8
  4. (4) Brigham and Women's Hospital, grid.62560.37
  5. (5) Harvard University, grid.38142.3c
  6. (6) University of Michigan, grid.214458.e
  7. (7) GlaxoSmithKline (United Kingdom), grid.418236.a
  8. (8) Queen Mary University of London, grid.4868.2
  9. (9) deCODE Genetics/Amgen, Inc., Reykjavik, Iceland
  10. (10) Institute of Metabolic Science, grid.470900.a
  11. (11) Medical Research Institute, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK
  12. (12) Helmholtz Zentrum München, grid.4567.0
  13. (13) Karolinska University Hospital, grid.24381.3c
  14. (14) Karolinska Institute, grid.4714.6
  15. (15) Umeå University, grid.12650.30
  16. (16) Lund University, grid.4514.4
  17. (17) Queen's University Belfast, grid.4777.3
  18. (18) National Institute on Aging, grid.419475.a
  19. (19) Imperial College London, grid.7445.2
  20. (20) Paris Cardiovascular Research Center, grid.462416.3
  21. (21) Paris Descartes University, grid.10992.33
  22. (22) National Institute for Health and Welfare, grid.14758.3f
  23. (23) University of Helsinki, grid.7737.4
  24. (24) University College London, grid.83440.3b
  25. (25) Heidelberg University, grid.7700.0
  26. (26) Los Angeles Biomedical Research Institute, grid.279946.7
  27. (27) Tampere University, grid.502801.e
  28. (28) University of Verona, grid.5611.3
  29. (29) Uppsala University, grid.8993.b
  30. (30) University Medical Center Groningen, grid.4494.d
  31. (31) Stanford University, grid.168010.e
  32. (32) National and Kapodistrian University of Athens, grid.5216.0
  33. (33) UCSF Benioff Children's Hospital, grid.414016.6
  34. (34) State Serum Institute, grid.6203.7
  35. (35) University of Copenhagen, grid.5254.6, KU
  36. (36) Broad Institute, grid.66859.34
  37. (37) Boston Children's Hospital, grid.2515.3
  38. (38) National Heart Lung and Blood Institute, grid.279885.9
  39. (39) Stanford Medicine, grid.240952.8
  40. (40) VU University Medical Center, grid.16872.3a
  41. (41) Korea National Institute of Health, grid.415482.e
  42. (42) University of Pennsylvania, grid.25879.31
  43. (43) University of North Carolina at Chapel Hill, grid.10698.36
  44. (44) Loyola University Chicago, grid.164971.c
  45. (45) Institute of Social and Preventive Medicine, grid.482968.9
  46. (46) HudsonAlpha Institute for Biotechnology, grid.417691.c
  47. (47) Erasmus University Medical Center, grid.5645.2
  48. (48) Centro Cardiologico Monzino, grid.418230.c
  49. (49) University of Milan, grid.4708.b
  50. (50) Centre for research in epidemiology and population health, grid.463845.8
  51. (51) Azienda Sanitaria di Firenze, grid.423864.f
  52. (52) NIHR Cambridge Biomedical Research Centre, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK
  53. (53) Wellcome Sanger Institute, grid.10306.34
  54. (54) University of Lincoln, grid.36511.30
  55. (55) University of Washington, grid.34477.33
  56. (56) The University of Texas Health Science Center at Houston, grid.267308.8
  57. (57) National Human Genome Research Institute, grid.280128.1
  58. (58) VU Amsterdam, grid.12380.38
  59. (59) TU Dresden, grid.4488.0
  60. (60) University of Lausanne, grid.9851.5
  61. (61) Imperial College Healthcare NHS Trust, grid.417895.6
  62. (62) Ealing Hospital NHS Trust, grid.412922.e
  63. (63) National Health Research Institutes, grid.59784.37
  64. (64) National University Health System, grid.410759.e
  65. (65) National University of Singapore, grid.4280.e
  66. (66) Duke NUS Graduate Medical School, grid.428397.3
  67. (67) Singapore National Eye Center, grid.419272.b
  68. (68) University of Dundee, Ninewells Hospital and Medical School, Dundee, UK
  69. (69) Institute of Epidemiology I, Helmholtz Zentrum München, Neuherberg, Germany
  70. (70) Pasteur Institute of Lille, grid.8970.6
  71. (71) University of Cambridge, grid.5335.0
  72. (72) University of Glasgow, grid.8756.c
  73. (73) University of Bristol, grid.5337.2
  74. (74) Hospital del Mar Medical Research Institute, grid.20522.37
  75. (75) Deutsches Zentrum für Herz Kreislauf Forschung (DZHK), partner site Hamburg, Lübeck, Kiel, Germany
  76. (76) University of Lübeck, grid.4562.5
  77. (77) University of Ioannina, grid.9594.1
  78. (78) University of Oxford, grid.4991.5
  79. (79) Hôpital Rangueil, grid.414295.f
  80. (80) University of the West Indies, grid.12916.3d
  81. (81) Synpromics, Ltd, Edinburgh, UK
  82. (82) University of Edinburgh, grid.4305.2
  83. (83) Istituto Neurologico Mediterraneo, grid.419543.e
  84. (84) University of Insubria, grid.18147.3b
  85. (85) Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, UK
  86. (86) Glenfield Hospital, grid.412925.9
  87. (87) Cedars-Sinai Medical Center, grid.50956.3f
  88. (88) University Hospital Regensburg, grid.411941.8
  89. (89) University of Regensburg, grid.7727.5
  90. (90) University of Iceland, grid.14013.37
  91. (91) Icelandic Heart Association, grid.420802.c
  92. (92) University of Oulu, grid.10858.34
  93. (93) Oulu University Hospital, grid.412326.0
  94. (94) Kuopion Liikuntalääketieteen Tutkimuslaitos, grid.419013.e
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  96. (96) Nutritional Epidemiology Research Unit, grid.464122.7
  97. (97) Poznan University of Medical Sciences, grid.22254.33
  98. (98) European Academy of Bozen, grid.418908.c
  99. (99) Norwegian University of Science and Technology, grid.5947.f
  100. (100) St Olav's University Hospital, grid.52522.32
  101. (101) University of Utah, grid.223827.e
  102. (102) Weill Cornell Medical College in Qatar, grid.416973.e
  103. (103) Hannover Medical School, grid.10423.34
  104. (104) Kaiser Permanente, grid.280062.e
  105. (105) Tampere University Hospital, grid.412330.7
  106. (106) Massachusetts General Hospital, grid.32224.35
  107. (107) Onassis Cardiac Surgery Center, grid.419873.0
  108. (108) MRC Unit for Lifelong Health and Ageing, grid.268922.5
  109. (109) Swiss Institute of Bioinformatics, grid.419765.8
  110. (110) Kuopio University Hospital, grid.410705.7
  111. (111) Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland
  112. (112) University of Eastern Finland, grid.9668.1
  113. (113) Office of Population Studies Foundation, Inc., Talamban, Cebu City, Philippines
  114. (114) University of San Carlos, grid.267101.3
  115. (115) Taichung Veterans General Hospital, grid.410764.0
  116. (116) National Yang Ming University, grid.260770.4
  117. (117) Boston University School of Medicine, grid.475010.7
  118. (118) European Genomic Institute for Diabetes, grid.452394.d
  119. (119) Integrated Genomics and Metabolic Diseases Modeling, grid.463858.4
  120. (120) University of Lille, grid.503422.2
  121. (121) Department of Medicine I, University Hospital Großhadern, Ludwig Maximilians University, Munich, Germany
  122. (122) Ludwig Maximilian University of Munich, grid.5252.0
  123. (123) Harokopio University, grid.15823.3d
  124. (124) Sorbonne University, grid.462844.8
  125. (125) King's College London, grid.13097.3c
  126. (126) University of Tartu, grid.10939.32
  127. (127) University of Maryland, Baltimore, grid.411024.2
  128. (128) Institute of Genetic and Biomedical Research, grid.428485.7
  129. (129) Leiden University Medical Center, grid.10419.3d
  130. (130) EMGO Institute for Health and Care Research, grid.466632.3
  131. (131) Ospedale di Bolzano, grid.415844.8
  132. (132) Group Health Cooperative, grid.280243.f
  133. (133) Washington University in St. Louis, grid.4367.6
  134. (134) Center for Non-Communicable Diseases, grid.497620.e
  135. (135) University of Greifswald, grid.5603.0
  136. (136) Ruddy Canadian Cardiovascular Genetics Centre, Ottawa, Ontario, Canada
  137. (137) University of Ottawa, grid.28046.38
  138. (138) South Karelia Central Hospital, grid.416155.2
  139. (139) Deutsches Zentrum für Herz Kreislauf Forschung (DZHK), Munich, Germany
  140. (140) German Heart Centre, grid.472754.7
  141. (141) Munich Heart Alliance, Munich, Germany
  142. (142) Technical University of Munich, grid.6936.a
  143. (143) National Defense Medical Center, grid.260565.2
  144. (144) Royal College of Surgeons in Ireland, grid.4912.e
  145. (145) University of Leicester, grid.9918.9
  146. (146) Isfahan University of Medical Sciences, grid.411036.1
  147. (147) Centre for Medical Systems Biology, grid.450025.6
  148. (148) Durrer Center for Cardiogenetic Research, ICIN–Netherlands Heart Institute, Utrecht, the Netherlands
  149. (149) Academic Medical Center, grid.5650.6
  150. (150) University Hospital of Lausanne, grid.8515.9
  151. (151) University of Strasbourg, grid.11843.3f
  152. (152) The Arctic University of Norway, grid.10919.30
  153. (153) Case Western Reserve University, grid.67105.35
  154. (154) Ministry of Health, grid.450284.f
  155. (155) Illumina (United States), grid.185669.5
  156. (156) German Center for Diabetes Research, grid.452622.5
  157. (157) Central Finland Health Care District, grid.460356.2
  158. (158) Danube University Krems, grid.15462.34
  159. (159) Dasman Diabetes Institute, grid.452356.3
  160. (160) King Abdulaziz University, grid.412125.1
  161. (161) Columbia University, grid.21729.3f
  162. (162) Medical University of Graz, grid.11598.34
  163. (163) Synlab (Germany), grid.461810.a
  164. (164) Icahn School of Medicine at Mount Sinai, grid.59734.3c
  165. (165) University of Liverpool, grid.10025.36

Description

To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure-associated loci, of which 17 were new; 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target organ damage in multiple tissues but with minor effects in the kidney. Our findings expand current knowledge of blood pressure-related pathways and highlight tissues beyond the classical renal system in blood pressure regulation.

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University of Copenhagen

Danish Open Access Indicator

2016: Unused

Research area: Medicine

Danish Bibliometrics Indicator

2016: Level 2

Research area: Medicine

Dimensions Citation Indicators

Times Cited: 208

Field Citation Ratio (FCR): 78.17

Relative Citation ratio (RCR): 12.61

Open Access Info

Green, Published