Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals

Publication type

Journal Article

Authors

  1. Praveen Surendran
  2. Elena V. Feofanova
  3. Najim Lahrouchi
  4. Ioanna Ntalla
  5. Savita Karthikeyan
  6. James Cook
  7. Lingyan Chen
  8. Borbala Mifsud
  9. Chen Yao
  10. Aldi T. Kraja
  11. James H. Cartwright
  12. Jacklyn N. Hellwege
  13. Ayush Giri
  14. Vinicius Tragante
  15. Gudmar Thorleifsson
  16. Dajiang J. Liu
  17. Bram P. Prins
  18. Isobel D. Stewart
  19. Claudia P. Cabrera
  20. James M. Eales
  21. Artur Akbarov
  22. Paul L. Auer
  23. Lawrence F. Bielak
  24. Joshua C. Bis
  25. Vickie S. Braithwaite
  26. Jennifer A. Brody
  27. E. Warwick Daw
  28. Helen R. Warren
  29. Fotios Drenos
  30. Sune Fallgaard Nielsen
  31. Jessica D. Faul
  32. Eric B. Fauman
  33. Cristiano Fava
  34. Teresa Ferreira
  35. Christopher N. Foley
  36. Nora Franceschini
  37. He Gao
  38. Olga Giannakopoulou
  39. Franco Giulianini
  40. Daniel F. Gudbjartsson
  41. Xiuqing Guo
  42. Sarah E. Harris
  43. Aki S. Havulinna
  44. Anna Helgadottir
  45. Jennifer E. Huffman
  46. Shih-Jen Hwang
  47. Stavroula Kanoni
  48. Jukka Kontto
  49. Martin G. Larson
  50. Ruifang Li-Gao
  51. Jaana Lindström
  52. Luca A. Lotta
  53. Yingchang Lu
  54. Jian’an Luan
  55. Anubha Mahajan
  56. Giovanni Malerba
  57. Nicholas G. D. Masca
  58. Hao Mei
  59. Cristina Menni
  60. Dennis O. Mook-Kanamori
  61. David Mosen-Ansorena
  62. Martina Müller-Nurasyid
  63. Guillaume Paré
  64. Dirk S. Paul
  65. Markus Perola
  66. Alaitz Poveda
  67. Rainer Rauramaa
  68. Melissa Richard
  69. Tom G. Richardson
  70. Nuno Sepúlveda
  71. Xueling Sim
  72. Albert V. Smith
  73. Jennifer A. Smith
  74. James R. Staley
  75. Alena Stanáková
  76. Patrick Sulem
  77. Sébastien Thériault
  78. Unnur Thorsteinsdottir
  79. Stella Trompet
  80. Tibor V. Varga
  81. Digna R. Velez Edwards
  82. Giovanni Veronesi
  83. Stefan Weiss
  84. Sara M. Willems
  85. Jie Yao
  86. Robin Young
  87. Bing Yu
  88. Weihua Zhang
  89. Jing-Hua Zhao
  90. Wei Zhao
  91. Evangelos Evangelou
  92. Stefanie Aeschbacher
  93. Eralda Asllanaj
  94. Stefan Blankenberg
  95. Lori L. Bonnycastle
  96. Jette Bork-Jensen
  97. Ivan Brandslund
  98. Peter S. Braund
  99. Stephen Burgess
  100. Kelly Cho
  101. Cramer Christensen
  102. John Connell
  103. Renée de Mutsert
  104. Anna F. Dominiczak
  105. Marcus Dörr
  106. Gudny Eiriksdottir
  107. Aliki-Eleni Farmaki
  108. J. Michael Gaziano
  109. Niels Grarup
  110. Megan L. Grove
  111. Göran Hallmans
  112. Torben Hansen
  113. Christian T. Have
  114. Gerardo Heiss
  115. Marit E. Jørgensen
  116. Pekka Jousilahti
  117. Eero Kajantie
  118. Mihir Kamat
  119. AnneMari Käräjämäki
  120. Fredrik Karpe
  121. Heikki A. Koistinen
  122. Csaba P. Kovesdy
  123. Kari Kuulasmaa
  124. Tiina Laatikainen
  125. Lars Lannfelt
  126. I-Te Lee
  127. Wen-Jane Lee
  128. Allan Linneberg
  129. Lisa W. Martin
  130. Marie Moitry
  131. Girish Nadkarni
  132. Matt J. Neville
  133. Colin N.A. Palmer
  134. George J. Papanicolaou
  135. Oluf Pedersen
  136. James Peters
  137. Neil Poulter
  138. Asif Rasheed
  139. Katrine L. Rasmussen
  140. N. William Rayner
  141. Reedik Mägi
  142. Frida Renström
  143. Rainer Rettig
  144. Jacques Rossouw
  145. Pamela J. Schreiner
  146. Peter S. Sever
  147. Emil L. Sigurdsson
  148. Tea Skaaby
  149. Yan V. Sun
  150. Johan Sundstrom
  151. Gudmundur Thorgeirsson
  152. Tõnu Esko
  153. Elisabetta Trabetti
  154. Philip S. Tsao
  155. Tiinamaija Tuomi
  156. Stephen T. Turner
  157. Ioanna Tzoulaki
  158. Ilonca Vaartjes
  159. Anne-Claire Vergnaud
  160. Cristen J. Willer
  161. Peter W. F. Wilson
  162. Daniel R. Witte
  163. Ekaterina Yonova-Doing
  164. He Zhang
  165. Aliya Naheed
  166. Peter Almgren
  167. Philippe Amouyel
  168. Folkert W. Asselbergs
  169. Michael R. Barnes
  170. Alexandra I. Blakemore
  171. Michael Boehnke
  172. Michiel L. Bots
  173. Erwin P. Bottinger
  174. Julie E. Buring
  175. John C. Chambers
  176. Yii-Der Ida Chen
  177. Rajiv Chowdhury
  178. David Conen
  179. Adolfo Correa
  180. George Davey Smith
  181. Rudolf A. de Boer
  182. Ian J. Deary
  183. George Dedoussis
  184. Panos Deloukas
  185. Emanuele Di Angelantonio
  186. Paul Elliott
  187. Stephan B. Felix
  188. Jean Ferrières
  189. Ian Ford
  190. Myriam Fornage
  191. Paul W. Franks
  192. Stephen Franks
  193. Philippe Frossard
  194. Giovanni Gambaro
  195. Tom R. Gaunt
  196. Leif Groop
  197. Vilmundur Gudnason
  198. Tamara B. Harris
  199. Caroline Hayward
  200. Branwen J. Hennig
  201. Karl-Heinz Herzig
  202. Erik Ingelsson
  203. Jaakko Tuomilehto
  204. Marjo-Riitta Järvelin
  205. J. Wouter Jukema
  206. Sharon L.R. Kardia
  207. Frank Kee
  208. Jaspal S. Kooner
  209. Charles Kooperberg
  210. Lenore J. Launer
  211. Lars Lind
  212. Ruth J.F. Loos
  213. Abdulla al Shafi Majumder
  214. Markku Laakso
  215. Mark I. McCarthy
  216. Olle Melander
  217. Karen L. Mohlke
  218. Alison D. Murray
  219. Børge Grønne Nordestgaard
  220. Marju Orho-Melander
  221. Chris J. Packard
  222. Sandosh Padmanabhan
  223. Walter Palmas
  224. Ozren Polasek
  225. David J. Porteous
  226. Andrew M. Prentice
  227. Michael A. Province
  228. Caroline L. Relton
  229. Kenneth Rice
  230. Paul M. Ridker
  231. Olov Rolandsson
  232. Frits R. Rosendaal
  233. Jerome I. Rotter
  234. Igor Rudan
  235. Veikko Salomaa
  236. Nilesh J. Samani
  237. Naveed Sattar
  238. Wayne H.-H. Sheu
  239. Blair H. Smith
  240. Nicole Soranzo
  241. Timothy D. Spector
  242. John M. Starr
  243. Sylvain Sebert
  244. Kent D. Taylor
  245. Timo A. Lakka
  246. Nicholas J. Timpson
  247. Martin D. Tobin
  248. Pim van der Harst
  249. Peter van der Meer
  250. Vasan S. Ramachandran
  251. Niek Verweij
  252. Jarmo Virtamo
  253. Uwe Völker
  254. David R. Weir
  255. Eleftheria Zeggini
  256. Fadi J. Charchar
  257. Nicholas J. Wareham
  258. Claudia Langenberg
  259. Maciej Tomaszewski
  260. Adam S. Butterworth
  261. Mark J. Caulfield
  262. John Danesh
  263. Todd L. Edwards
  264. Hilma Holm
  265. Adriana M. Hung
  266. Cecilia M. Lindgren
  267. Chunyu Liu
  268. Alisa K. Manning
  269. Andrew P. Morris
  270. Alanna C. Morrison
  271. Christopher J. O’Donnell
  272. Bruce M. Psaty
  273. Danish Saleheen
  274. Kari Stefansson
  275. Eric Boerwinkle
  276. Daniel I. Chasman
  277. Daniel Levy
  278. Christopher Newton-Cheh
  279. Patricia B. Munroe
  280. Joanna M. M. Howson

Publication date

November 23, 2020

Summary:

Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to ~1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency ≤ 0.01) variant BP associations (P < 5 × 10−8), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were ~8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.

Published in

Nature Genetics

DOI

https://doi.org/10.1038/s41588-020-00713-x

ISSN

10614036

Subjects

Link

- https://lib.essex.ac.uk/iii/encore/record/C__Rb1680801

Notes

Online Early

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