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Journal Article

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

Authors

  1. Georg B. Ehret
  2. Teresa Ferreira
  3. Daniel I. Chasman
  4. Anne U. Jackson
  5. Ellen M. Schmidt
  6. Toby Johnson
  7. Gudmar Thorleifsson
  8. Jian'an Luan
  9. Louise A. Donnelly
  10. Stavroula Kanoni
  11. Ann-Kristin Petersen
  12. Vasyl Pihur
  13. Rona J. Strawbridge
  14. Dmitry Shungin
  15. Maria F. Hughes
  16. Osorio Meirelles
  17. Marika Kaakinen
  18. Nabila Bouatia-Naji
  19. Kati Kristiansson
  20. Sonia Shah
  21. Marcus E. Kleber
  22. Xiuqing Guo
  23. Leo-Pekka Lyytikäinen
  24. Cristiano Fava
  25. Niclas Eriksson
  26. Ilja M. Nolte
  27. Patrik K. Magnusson
  28. Elias L. Salfati
  29. Loukianos S. Rallidis
  30. Elizabeth Theusch
  31. Andrew J. P. Smith
  32. Lasse Folkersen
  33. Kate Witkowska
  34. Tune H. Pers
  35. Roby Joehanes
  36. Stuart K. Kim
  37. Lazaros Lataniotis
  38. Rick Jansen
  39. Andrew D. Johnson
  40. Helen Warren
  41. Young Jin Kim
  42. Wei Zhao
  43. Ying Wu
  44. Bamidele O. Tayo
  45. Murielle Bochud
  46. Devin Absher
  47. Linda S. Adair
  48. Najaf Amin
  49. Dan E. Arking
  50. Tomas Axelsson
  51. Damiano Baldassarre
  52. Beverley Balkau
  53. Stefania Bandinelli
  54. Michael R. Barnes
  55. Inês Barroso
  56. Stephen Bevan
  57. Joshua C. Bis
  58. Gyda Bjornsdottir
  59. Michael Boehnke
  60. Eric Boerwinkle
  61. Lori L. Bonnycastle
  62. Dorret I. Boomsma
  63. Stefan R. Bornstein
  64. Morris J. Brown
  65. Michel Burnier
  66. Claudia P. Cabrera
  67. John C. Chambers
  68. I. Shou Chang
  69. Ching-Yu Cheng
  70. Peter S. Chines
  71. Ren-Hua Chung
  72. Francis S. Collins
  73. John M. Connell
  74. Angela Döring
  75. Jean Dallongeville
  76. John Danesh
  77. Ulf de Faire
  78. Graciela Delgado
  79. Anna F. Dominiczak
  80. Alex S. F. Doney
  81. Fotios Drenos
  82. Sarah Edkins
  83. John D. Eicher
  84. Roberto Elosua
  85. Stefan Enroth
  86. Jeanette Erdmann
  87. Per Eriksson
  88. Tonu Esko
  89. Evangelos Evangelou
  90. Alun Evans
  91. Tove Fall
  92. Martin Farrall
  93. Janine F. Felix
  94. Jean Ferrières
  95. Luigi Ferrucci
  96. Myriam Fornage
  97. Terrence Forrester
  98. Nora Franceschini
  99. Oscar H. Franco
  100. Anders Franco-Cereceda
  101. Ross M. Fraser
  102. Santhi K. Ganesh
  103. He Gao
  104. Karl Gertow
  105. Francesco Gianfagna
  106. Bruna Gigante
  107. Franco Giulianini
  108. Anuj Goel
  109. Alison H. Goodall
  110. Mark O. Goodarzi
  111. Mathias Gorski
  112. Jürgen Gräßler
  113. Christopher J. Groves
  114. Vilmundur Gudnason
  115. Ulf Gyllensten
  116. Göran Hallmans
  117. Anna-Liisa Hartikainen
  118. Maija Hassinen
  119. Aki S. Havulinna
  120. Caroline Hayward
  121. Serge Hercberg
  122. Karl-Heinz Herzig
  123. Andrew A. Hicks
  124. Aroon D. Hingorani
  125. Joel N. Hirschhorn
  126. Albert Hofman
  127. Jostein Holmen
  128. Oddgeir Lingaas Holmen
  129. Jouke-Jan Hottenga
  130. Phil Howard
  131. Chao A. Hsiung
  132. Steven C. Hunt
  133. M. Arfan Ikram
  134. Thomas Illig
  135. Carlos Iribarren
  136. Richard A. Jensen
  137. Mika Kähönen
  138. Hyun Min Kang
  139. Sekar Kathiresan
  140. Brendan J. Keating
  141. Kay-Tee Khaw
  142. Yun Kyoung Kim
  143. Eric Kim
  144. Mika Kivimaki
  145. Norman Klopp
  146. Genovefa Kolovou
  147. Pirjo Komulainen
  148. Jaspal S. Kooner
  149. Gulum Kosova
  150. Ronald M. Krauss
  151. Diana Kuh
  152. Zoltan Kutalik
  153. Johanna Kuusisto
  154. Kirsti Kvaløy
  155. Timo A. Lakka
  156. Nanette R. Lee
  157. I. Te Lee
  158. Wen-Jane Lee
  159. Daniel Levy
  160. Xiaohui Li
  161. Kae-Woei Liang
  162. Honghuang Lin
  163. Li Lin
  164. Jaana Lindström
  165. Stéphane Lobbens
  166. Satu Männistö
  167. Gabriele Müller
  168. Martina Müller-Nurasyid
  169. François Mach
  170. Hugh S. Markus
  171. Eirini Marouli
  172. Mark I. McCarthy
  173. Colin A. McKenzie
  174. Pierre Meneton
  175. Cristina Menni
  176. Andres Metspalu
  177. Vladan Mijatovic
  178. Leena Moilanen
  179. May E. Montasser
  180. Andrew D. Morris
  181. Alanna C. Morrison
  182. Antonella Mulas
  183. Ramaiah Nagaraja
  184. Narisu Narisu
  185. Kjell Nikus
  186. Christopher J. O'Donnell
  187. Paul F. O'Reilly
  188. Ken K. Ong
  189. Fred Paccaud
  190. Cameron D. Palmer
  191. Afshin Parsa
  192. Nancy L. Pedersen
  193. Brenda W. Penninx
  194. Markus Perola
  195. Annette Peters
  196. Neil Poulter
  197. Peter P. Pramstaller
  198. Bruce M. Psaty
  199. Thomas Quertermous
  200. Dabeeru C. Rao
  201. Asif Rasheed
  202. N. William Rayner
  203. Frida Renström
  204. Rainer Rettig
  205. Kenneth M. Rice
  206. Robert Roberts
  207. Lynda M. Rose
  208. Jacques Rossouw
  209. Nilesh J. Samani
  210. Serena Sanna
  211. Jouko Saramies
  212. Heribert Schunkert
  213. Sylvain Sebert
  214. Wayne H. H. Sheu
  215. Young-Ah Shin
  216. Xueling Sim
  217. Johannes H. Smit
  218. Albert V. Smith
  219. Maria X. Sosa
  220. Tim D. Spector
  221. Alena Stančáková
  222. Alice V. Stanton
  223. Kathleen E. Stirrups
  224. Heather M. Stringham
  225. Johan Sundstrom
  226. Amy J. Swift
  227. Ann-Christine Syvänen
  228. E. Shyong Tai
  229. Toshiko Tanaka
  230. Kirill V. Tarasov
  231. Alexander Teumer
  232. Unnur Thorsteinsdottir
  233. Martin D. Tobin
  234. Elena Tremoli
  235. Andre G. Uitterlinden
  236. Matti Uusitupa
  237. Ahmad Vaez
  238. Dhananjay Vaidya
  239. Cornelia M. van Duijn
  240. Erik P. A. van Iperen
  241. Ramachandran S. Vasan
  242. Germaine C. Verwoert
  243. Jarmo Virtamo
  244. Veronique Vitart
  245. Benjamin F. Voight
  246. Peter Vollenweider
  247. Aline Wagner
  248. Louise V. Wain
  249. Nicholas J. Wareham
  250. Hugh Watkins
  251. Alan B. Weder
  252. Harm-Jan Westra
  253. Rainford Wilks
  254. Tom Wilsgaard
  255. James F. Wilson
  256. Tien Y. Wong
  257. Tsun-Po Yang
  258. Jie Yao
  259. Loic Yengo
  260. Weihua Zhang
  261. Jing Hua Zhao
  262. Xiaofeng Zhu
  263. Pascal Bovet
  264. Richard S. Cooper
  265. Karen L. Mohlke
  266. Danish Saleheen
  267. Jong-Young Lee
  268. Paul Elliott
  269. Hinco J. Gierman
  270. Cristen J. Willer
  271. Lude Franke
  272. G. Kees Hovingh
  273. Kent D. Taylor
  274. George Dedoussis
  275. Peter Sever
  276. Andrew Wong
  277. Lars Lind
  278. Themistocles L. Assimes
  279. Inger Njølstad
  280. Peter E. H. Schwarz
  281. Claudia Langenberg
  282. Harold Snieder
  283. Mark J. Caulfield
  284. Olle Melander
  285. Markku Laakso
  286. Juha Saltevo
  287. Rainer Rauramaa
  288. Jaakko Tuomilehto
  289. Erik Ingelsson
  290. Terho Lehtimäki
  291. Kristian Hveem
  292. Walter Palmas
  293. Winfried März
  294. Meena Kumari
  295. Veikko Salomaa
  296. Yii-Der I. Chen
  297. Jerome I. Rotter
  298. Philippe Froguel
  299. Marjo-Riitta Jarvelin
  300. Edward G. Lakatta
  301. Kari Kuulasmaa
  302. Paul W. Franks
  303. Anders Hamsten
  304. H. Erich Wichmann
  305. Colin N. A. Palmer
  306. Kari Stefansson
  307. Paul M. Ridker
  308. Ruth J. F. Loos
  309. Aravinda Chakravarti
  310. Panos Deloukas
  311. Andrew P. Morris
  312. Christopher Newton-Cheh
  313. Patricia B. Munroe

Publication date

2016

Summary

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.

Published in

Nature Genetics

Volume and page numbers

48 , 1171 -1184

DOI

https://dx.doi.org/10.1038/ng.3667

Subjects

Medicine, Science And Technology, Health, Biology, and Genetics

Links

University of Essex Research Repository - http://repository.essex.ac.uk/21503/; University of Essex, Albert Sloman Library Periodicals *restricted to University of Essex registered users* - http://serlib0.essex.ac.uk/record=b1680801~S5

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