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The Genetics of Blood Pressure Regulation and Its Target Organs From Association Studies in 342,415 Individuals Publisher Pubmed



Ehret GB1, 2 ; Ferreira T3 ; Chasman DI4, 5 ; Jackson AU6, 7 ; Schmidt EM8 ; Johnson T9, 10 ; Thorleifsson G11 ; Luan J12 ; Donnelly LA13 ; Kanoni S14 ; Petersen AK15 ; Pihur V1 ; Strawbridge RJ16, 17 ; Shungin D18, 19, 20 Show All Authors
Authors
  1. Ehret GB1, 2
  2. Ferreira T3
  3. Chasman DI4, 5
  4. Jackson AU6, 7
  5. Schmidt EM8
  6. Johnson T9, 10
  7. Thorleifsson G11
  8. Luan J12
  9. Donnelly LA13
  10. Kanoni S14
  11. Petersen AK15
  12. Pihur V1
  13. Strawbridge RJ16, 17
  14. Shungin D18, 19, 20
  15. Hughes MF21
  16. Meirelles O22
  17. Kaakinen M23
  18. Bouatianaji N24, 25
  19. Kristiansson K26, 27
  20. Shah S28
  21. Kleber ME29
  22. Guo X30
  23. Lyytikainen LP31, 32
  24. Fava C33, 34
  25. Eriksson N35
  26. Nolte IM36
  27. Magnusson PK37
  28. Salfati EL38
  29. Rallidis LS39
  30. Theusch E40
  31. Smith AJP41
  32. Folkersen L16
  33. Witkowska K9, 42
  34. Pers TH43, 44, 45, 46, 47
  35. Joehanes R48
  36. Kim SK49
  37. Lataniotis L14
  38. Jansen R50
  39. Johnson AD48, 51
  40. Warren H9, 42
  41. Kim YJ52
  42. Zhao W53
  43. Wu Y54
  44. Tayo BO55
  45. Bochud M56
  46. Absher D57
  47. Adair LS58
  48. Amin N59
  49. Arking DE1
  50. Axelsson T60
  51. Baldassarre D61, 62
  52. Balkau B63
  53. Bandinelli S64
  54. Barnes MR14, 42
  55. Barroso I65, 66, 67
  56. Bevan S68
  57. Bis JC69
  58. Bjornsdottir G11
  59. Boehnke M6, 7
  60. Boerwinkle E70
  61. Bonnycastle LL71
  62. Boomsma DI72
  63. Bornstein SR73
  64. Brown MJ74
  65. Burnier M75
  66. Cabrera CP9, 42
  67. Chambers JC76, 77, 78
  68. Chang IS79
  69. Cheng CY80, 81, 82
  70. Chines PS71
  71. Chung RH83
  72. Collins FS71
  73. Connell JM84
  74. Doring A85, 86
  75. Dallongeville J87
  76. Danesh J65, 89
  77. De Faire U90
  78. Delgado G29
  79. Dominiczak AF91
  80. Doney ASF13
  81. Drenos F41, 92
  82. Edkins S65
  83. Eicher JD48, 51
  84. Elosua R93
  85. Enroth S94, 95
  86. Erdmann J96, 97
  87. Eriksson P16
  88. Esko T43, 98, 99
  89. Evangelou E76, 100
  90. Evans A21
  91. Fall T101
  92. Farrall M3, 102
  93. Felix JF103
  94. Ferrieres J104
  95. Ferrucci L105
  96. Fornage M106
  97. Forrester T107
  98. Franceschini N108
  99. Franco OH103
  100. Francocereceda A109
  101. Fraser RM110, 111
  102. Ganesh SK112
  103. Gao H76
  104. Gertow K16, 17
  105. Gianfagna F113, 114
  106. Gigante B90
  107. Giulianini F4
  108. Goel A3, 102
  109. Goodall AH115, 116
  110. Goodarzi MO117
  111. Gorski M118, 119
  112. Graler J120
  113. Groves CJ121
  114. Gudnason V122, 123
  115. Gyllensten U94, 95
  116. Hallmans G18
  117. Hartikainen AL124, 125
  118. Hassinen M126
  119. Havulinna AS26
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  121. Hercberg S128
  122. Herzig KH129, 130, 131
  123. Hicks AA132, 268
  124. Hingorani AD28
  125. Hirschhorn JN43, 44, 45, 133
  126. Hofman A103, 134
  127. Holmen J135
  128. Holmen OL135, 136
  129. Hottenga JJ72
  130. Howard P41
  131. Hsiung CA83
  132. Hunt SC137, 138
  133. Ikram MA103, 139, 140
  134. Illig T141, 142, 143
  135. Iribarren C144
  136. Jensen RA69
  137. Kahonen M146, 147
  138. Kang HM6, 7
  139. Kathiresan S45, 148, 149, 150, 151
  140. Keating BJ152, 153
  141. Khaw KT154
  142. Kim YK52
  143. Kim E30
  144. Kivimaki M28
  145. Klopp N141, 142
  146. Kolovou G155
  147. Komulainen P126
  148. Kooner JS77, 78, 156
  149. Kosova G99, 148, 149
  150. Krauss RM157
  151. Kuh D158
  152. Kutalik Z159, 160
  153. Kuusisto J161
  154. Kvaloy K135
  155. Lakka TA126, 162, 163
  156. Lee NR164, 165
  157. Lee IT166, 167
  158. Lee WJ168
  159. Levy D48, 169
  160. Li X30
  161. Liang KW170, 171
  162. Lin H48, 172
  163. Lin L2
  164. Lindstrom J26
  165. Lobbens S173, 174, 175
  166. Mannisto S26
  167. Muller G176
  168. Mullernurasyid M15, 177, 178
  169. Mach F2
  170. Markus HS179
  171. Marouli E14, 180
  172. Mccarthy MI3, 121
  173. Mckenzie CA107
  174. Meneton P181
  175. Menni C182
  176. Metspalu A98
  177. Mijatovic V183
  178. Moilanen L184, 185
  179. Montasser ME186
  180. Morris AD13
  181. Morrison AC187
  182. Mulas A188
  183. Nagaraja R22
  184. Narisu N71
  185. Nikus K189, 190
  186. Odonnell CJ48, 151, 191
  187. Oreilly PF192
  188. Ong KK12
  189. Paccaud F56
  190. Palmer CD43, 45, 193
  191. Parsa A186
  192. Pedersen NL37
  193. Penninx BW194, 195, 196
  194. Perola M26, 27, 98
  195. Peters A86
  196. Poulter N197
  197. Pramstaller PP132, 198, 199
  198. Psaty BM70, 200, 201, 202
  199. Quertermous T38
  200. Rao DC203
  201. Rasheed A204
  202. Rayner NW3, 65, 121
  203. Renstrom F18, 19, 205
  204. Rettig R206
  205. Rice KM207
  206. Roberts R208, 209
  207. Rose LM4
  208. Rossouw J191
  209. Samani NJ115, 116
  210. Sanna S188
  211. Saramies J210
  212. Schunkert H211, 212, 213, 214
  213. Sebert S130, 163, 215
  214. Sheu WHH166, 167, 216
  215. Shin YA52
  216. Sim X6, 7, 217
  217. Smit JH194
  218. Smith AV122, 123
  219. Sosa MX1
  220. Spector TD182
  221. Stancakova A218
  222. Stanton AV219
  223. Stirrups KE14, 220
  224. Stringham HM6, 7
  225. Sundstrom J60
  226. Swift AJ71
  227. Syvanen AC60
  228. Tai ES81, 217, 221
  229. Tanaka T105
  230. Tarasov KV222
  231. Teumer A223
  232. Thorsteinsdottir U11, 123
  233. Tobin MD224
  234. Tremoli E61, 62
  235. Uitterlinden AG103, 225
  236. Uusitupa M226, 227
  237. Vaez A36, 228
  238. Vaidya D229
  239. Van Duijn CM103, 230
  240. Van Iperen EPA231, 232
  241. Vasan RS48, 233, 234
  242. Verwoert GC103
  243. Virtamo J26
  244. Vitart V127
  245. Voight BF235
  246. Vollenweider P236
  247. Wagner A237
  248. Wain LV224
  249. Wareham NJ12
  250. Watkins H3, 102
  251. Weder AB238
  252. Westra HJ239
  253. Wilks R240
  254. Wilsgaard T241, 242
  255. Wilson JF110, 127
  256. Wong TY80, 81, 82
  257. Yang TP14, 243
  258. Yao J30
  259. Yengo L173, 174, 175
  260. Zhang W76, 77
  261. Zhao JH12
  262. Zhu X244
  263. Bovet P56, 245
  264. Cooper RS55
  265. Mohlke KL54
  266. Saleheen D204, 246
  267. Lee JY52
  268. Elliott P76, 247
  269. Gierman HJ49, 248
  270. Willer CJ8, 238, 249
  271. Franke L250
  272. Hovingh GK251
  273. Taylor KD30
  274. Dedoussis G180
  275. Sever P197
  276. Wong A158
  277. Lind L60
  278. Assimes TL38
  279. Njolstad I241, 242
  280. Schwarz PEH73, 252, 253
  281. Langenberg C12
  282. Snieder H36
  283. Caulfield MJ9, 42
  284. Melander O33
  285. Laakso M161
  286. Saltevo J254
  287. Rauramaa R126, 163
  288. Tuomilehto J26, 255, 256, 257
  289. Ingelsson E38, 101
  290. Lehtimaki T31, 32
  291. Hveem K135
  292. Palmas W258
  293. Marz W259, 260
  294. Kumari M28
  295. Salomaa V26
  296. Chen YDI30
  297. Rotter JI30
  298. Froguel P121, 173, 174, 175
  299. Jarvelin MR131, 215, 247, 261
  300. Lakatta EG222
  301. Kuulasmaa K26
  302. Franks PW18, 19, 262
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  304. Wichmann HE85, 178, 263
  305. Palmer CNA13
  306. Stefansson K11, 123
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Source: Nature Genetics Published:2016


Abstract

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. © 2016 Nature America, Inc. All rights reserved.
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