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Genome-Wide Association Analysis Identifies Novel Blood Pressure Loci and Offers Biological Insights Into Cardiovascular Risk Publisher Pubmed



Warren HR1, 2 ; Evangelou E3, 4 ; Cabrera CP1, 2 ; Gao H3, 5 ; Ren M1, 2, 147 ; Mifsud B1 ; Ntalla I1 ; Surendran P6 ; Liu C7, 8 ; Cook JP9 ; Kraja AT10 ; Drenos F11, 12 ; Loh M3, 13 ; Verweij N14, 16 Show All Authors
Authors
  1. Warren HR1, 2
  2. Evangelou E3, 4
  3. Cabrera CP1, 2
  4. Gao H3, 5
  5. Ren M1, 2, 147
  6. Mifsud B1
  7. Ntalla I1
  8. Surendran P6
  9. Liu C7, 8
  10. Cook JP9
  11. Kraja AT10
  12. Drenos F11, 12
  13. Loh M3, 13
  14. Verweij N14, 16
  15. Marten J17
  16. Karaman I3
  17. Segura Lepe MP3, 18
  18. Oreilly PF19
  19. Knight J20
  20. Snieder H21
  21. Kato N22
  22. He J23
  23. Shyong Tai E24, 25
  24. Abdullah Said M14
  25. Porteous D26
  26. Alver M27, 174
  27. Poulter N28
  28. Farrall M29, 86
  29. Gansevoort RT30
  30. Padmanabhan S31, 108, 140
  31. Magi R27, 174
  32. Stanton A32
  33. Connell J33
  34. Bakker SJL34
  35. Metspalu A27, 174
  36. Shields DC35
  37. Thom S36, 160
  38. Brown M1, 2
  39. Sever P36
  40. Esko T15, 27, 62, 174
  41. Hayward C17, 108
  42. Van Der Harst P14
  43. Saleheen D37, 38
  44. Chowdhury R6
  45. Chambers JC3, 39, 40, 41, 47
  46. Chasman DI42, 43
  47. Chakravarti A44
  48. Newtoncheh C15, 16
  49. Lindgren CM15, 45, 46
  50. Levy D7, 8
  51. Kooner JS36, 40, 47, 48
  52. Keavney B49, 50
  53. Tomaszewski M49, 50
  54. Samani NJ51, 52
  55. Howson JMM6
  56. Tobin MD53
  57. Munroe PB1, 2
  58. Ehret GB44, 54
  59. Wain LV53
  60. Barnes MR1, 2
  61. Tzoulaki I3, 5
  62. Caulfield MJ1, 2
  63. Elliott P3, 5
  64. Wain V53
  65. Vaez A21, 55
  66. Jansen R56
  67. Joehanes R8, 57
  68. Van Der Most PJ21
  69. Mesut Erzurumluoglu A53
  70. Rose LM42
  71. Verwoert GC58
  72. Hottenga JJ59
  73. Strawbridge RJ60, 61
  74. Arking DE44
  75. Hwang SJ64, 65
  76. Guo X66
  77. Kutalik Z67, 68
  78. Trompet S69, 70
  79. Shrine N53
  80. Teumer A71, 72
  81. Ried JS73
  82. Bis JC74
  83. Smith AV75, 76
  84. Amin N77
  85. Nolte IM21
  86. Lyytikainen LP78, 79
  87. Mahajan A45
  88. Wareham NJ80
  89. Hofer E81, 82
  90. Joshi PK83
  91. Kristiansson K84
  92. Traglia M85
  93. Havulinna AS84
  94. Goel A45, 86
  95. Nalls MA87, 88
  96. Sober S89
  97. Vuckovic D90, 91
  98. Luan J80
  99. Fabiola Del Greco M92, 93
  100. Ayers KL94
  101. Marrugat J95
  102. Ruggiero D96
  103. Lopez LM97, 98
  104. Niiranen T84
  105. Enroth S99
  106. Jackson AU100
  107. Nelson CP51, 52
  108. Huffman JE17
  109. Zhang W3, 47
  110. Gandin I91
  111. Harris SE26, 97
  112. Zemonik T101
  113. Lu Y102
  114. Shah N103, 104
  115. De Borst MH34
  116. Mangino M105, 106
  117. Prins BP107
  118. Campbell A26, 108
  119. Ligao R109
  120. Chauhan G110, 111
  121. Oldmeadow C112
  122. Abecasis G113
  123. Abedi M114
  124. Barbieri CM85
  125. Batini C53
  126. Blake T53
  127. Boehnke M100
  128. Bottinger EP102
  129. Braund PS51, 52
  130. Brumat M91
  131. Campbell H83
  132. Cocca M91
  133. Collins F115
  134. Cordell HJ116
  135. Damman JJ117
  136. Davies G97, 118
  137. De Geus EJ59
  138. De Mutsert R109
  139. Deelen J119
  140. Demirkale Y120
  141. Doney ASF103
  142. Dorr M72, 121
  143. Ferreira T45
  144. Franberg M60, 61, 122
  145. Giedraitis V123
  146. Gieger C124
  147. Giulianini F42
  148. Gow AJ97, 125
  149. Hamsten A60, 61
  150. Harris TB126
  151. Hofman A58, 127
  152. Holliday EG112
  153. Jarvelin MR5, 128, 129
  154. Johansson A99
  155. Johnson AD8, 130
  156. Jousilahti P84
  157. Jula A84
  158. Kahonen M131, 132
  159. Kathiresan S15, 16
  160. Khaw KT38
  161. Kolcic I133
  162. Koskinen S84
  163. Langenberg C80
  164. Larson M8
  165. Launer LJ126
  166. Lehne B3
  167. Liewald DCM97, 118
  168. Lin L54
  169. Lind L134
  170. Mach F54
  171. Mamasoula C135
  172. Menni C105
  173. Milaneschi Y136
  174. Morgan A91
  175. Morris AD137
  176. Morrison AC138
  177. Munson PJ120
  178. Nandakumar P44
  179. Nguyen QT120
  180. Nutile T96
  181. Oldehinkel AJ139
  182. Oostra BA77
  183. Org E27, 174
  184. Palotie A141
  185. Pare G142
  186. Pattie A118
  187. Penninx BWJH136
  188. Pramstaller PP92, 93, 143, 144
  189. Raitakari OT145, 146
  190. Rice K148
  191. Ridker PM42, 43
  192. Riese H139
  193. Ripatti S141
  194. Robino A149
  195. Rotter JI66, 150
  196. Rudan I83
  197. Saba Y151
  198. Saint Pierre A92, 93, 152
  199. Sala CF85
  200. Sarin AP141
  201. Schmidt R81
  202. Scott R112, 153, 154
  203. Seelen MA34
  204. Siscovick D155
  205. Sorice R96, 156
  206. Stott DJ31
  207. Sundstrom J134
  208. Swertz M157
  209. Taylor KD158, 159
  210. Tzourio C110, 111, 161
  211. Uitterlinden AG58, 162
  212. Volker U72, 163
  213. Vollenweider P164
  214. Wild S83
  215. Willemsen G59
  216. Wright AF17
  217. Yao J66
  218. Theriault S142
  219. Conen D165
  220. John A112, 153, 154
  221. Debette S110, 111, 166
  222. Mookkanamori DO109, 167
  223. Zeggini E107
  224. Spector TD105
  225. Palmer CNA103
  226. Vergnaud AC3
  227. Loos RJF81, 102, 168
  228. Polasek O133
  229. Starr JM97, 169
  230. Girotto G90, 91
  231. Vitart V17
  232. Tuomilehto J170, 171
  233. Gyllensten U99
  234. Knekt P84
  235. Deary IJ97, 118
  236. Ciullo M96, 156
  237. Elosua R95
  238. Hicks AA92, 93
  239. Scott RA80
  240. Gasparini P90, 91
  241. Laan M89, 172
  242. Liu YM173
  243. Watkins H45, 86
  244. Hartman CA139
  245. Salomaa V84
  246. Toniolo D85
  247. Perola M27, 83, 141, 174
  248. Wilson JF17, 83
  249. Schmidt H151, 175
  250. Zhao JH80
  251. Lehtimaki T78, 79
  252. Van Duijn CM77
  253. Gudnason V75, 76
  254. Psaty BM74, 176, 177
  255. Peters A73
  256. Rettig R178
  257. James A179, 180
  258. Wouter Jukema J69
  259. Strachan DP181
  260. Palmas W182
  261. Ingelsson E183, 184
  262. Boomsma DI59
  263. Franco OH58
  264. Bochud M67
  265. Morris AP9, 45

Source: Nature Genetics Published:2017


Abstract

Elevated blood pressure is the leading heritable risk factor for cardiovascular disease worldwide. We report genetic association of blood pressure (systolic, diastolic, pulse pressure) among UK Biobank participants of European ancestry with independent replication in other cohorts, and robust validation of 107 independent loci. We also identify new independent variants at 11 previously reported blood pressure loci. In combination with results from a range of in silico functional analyses and wet bench experiments, our findings highlight new biological pathways for blood pressure regulation enriched for genes expressed in vascular tissues and identify potential therapeutic targets for hypertension. Results from genetic risk score models raise the possibility of a precision medicine approach through early lifestyle intervention to offset the impact of blood pressure-raising genetic variants on future cardiovascular disease risk.
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