Novel blood pressure locus and gene discovery using GWAS and expression datasets from blood and the kidney

Publication type

Journal Article

Authors

  1. Louise Wain
  2. Ahmad Vaez
  3. Rick Jansen
  4. Roby Joehanes
  5. Peter J. van der Most
  6. A. Mesut Erzurumluoglu
  7. Paul O'Reilly
  8. Claudia P. Cabrera
  9. Helen R. Warren
  10. Lynda M. Rose
  11. Germaine C. Verwoert
  12. Jouke-Jan Hottenga
  13. Rona J. Strawbridge
  14. Tonu Esko
  15. Dan E. Arking
  16. Shih-Jen Hwang
  17. Xiuqing Guo
  18. Zoltán Kutalik
  19. Stella Trompet
  20. Nick Shrine
  21. Alexander Teumer
  22. Janina S. Ried
  23. Joshua C. Bis
  24. Albert V. Smith
  25. Najaf Amin
  26. Ilja M. Nolte
  27. Leo-Pekka Lyytikainen
  28. Anubha Mahajan
  29. Nicholas J. Wareham
  30. Edith Hofer
  31. Peter K. Joshi
  32. Kati Kristiansson
  33. Michela Traglia
  34. Aki S. Havulinna
  35. Anuj Goel
  36. Mike A. Nalls
  37. Siim Sõber
  38. Dragana Vuckovic
  39. Jian'an Luan
  40. Fabiola Del Greco M
  41. Kristin L. Ayers
  42. Jaume Marrugat
  43. Daniela Ruggiero
  44. Lorna M. Lopez
  45. Teemu Niiranen
  46. Stefan Enroth
  47. Anne U. Jackson
  48. Christopher P. Nelson
  49. Jennifer E. Huffman
  50. Weihua Zhang
  51. Jonathan Marten
  52. Ilaria Gandin
  53. Sarah E. Harris
  54. Tatijana Zemonik
  55. Yingchang Lu
  56. Evangelos Evangelou
  57. Nabi Shah
  58. Martin H. de Borst
  59. Massimo Mangino
  60. Bram P. Prins
  61. Archie Campbell
  62. Ruifang Li-Gao
  63. Ganesh Chauhan
  64. Christopher Oldmeadow
  65. Goncalo Abecasis
  66. Maryam Abedi
  67. Caterina M. Barbieri
  68. Michael R. Barnes
  69. Chiara Batini
  70. John Beilby
  71. Tineka Blake
  72. Michael Boehnke
  73. Erwin P. Bottinger
  74. Peter S. Braund
  75. Morris Brown
  76. Marco Brumat
  77. Harry Campbell
  78. John C. Chambers
  79. Massimiliano Cocca
  80. Francis Collins
  81. John Connell
  82. Heather J. Cordell
  83. Jeffrey J. Damman
  84. Gail Davies
  85. Eco J. de Geus
  86. Renée de Mutsert
  87. Joris Deelen
  88. Yusuf Demirkale
  89. Alex S. F. Doney
  90. Marcus Dörr
  91. Martin Farrall
  92. Teresa Ferreira
  93. Mattias Frånberg
  94. He Gao
  95. Vilmantas Giedraitis
  96. Christian Gieger
  97. Franco Giulianini
  98. Alan J. Gow
  99. Anders Hamsten
  100. Tamara B. Harris
  101. Albert Hofman
  102. Elizabeth G. Holliday
  103. Jennie Hui
  104. Marjo-Riitta Jarvelin
  105. Åsa Johansson
  106. Andrew D. Johnson
  107. Pekka Jousilahti
  108. Antti Jula
  109. Mika Kähönen
  110. Sekar Kathiresan
  111. Kay-Tee Khaw
  112. Ivana Kolcic
  113. Seppo Koskinen
  114. Claudia Langenberg
  115. Marty Larson
  116. Lenore J. Launer
  117. Benjamin Lehne
  118. David C. M. Liewald
  119. Li Lin
  120. Lars Lind
  121. François Mach
  122. Chrysovalanto Mamasoula
  123. Cristina Menni
  124. Borbala Mifsud
  125. Yuri Milaneschi
  126. Anna Morgan
  127. Andrew D. Morris
  128. Alanna C. Morrison
  129. Peter J. Munson
  130. Priyanka Nandakumar
  131. Quang Tri Nguyen
  132. Teresa Nutile
  133. Albertine J. Oldehinkel
  134. Ben A. Oostra
  135. Elin Org
  136. Sandosh Padmanabhan
  137. Aarno Palotie
  138. Guillaume Pare
  139. Alison Pattie
  140. Brenda W. J. H. Penninx
  141. Neil Poulter
  142. Peter P. Pramstaller
  143. Olli T. Raitakari
  144. Meixia Ren
  145. Kenneth Rice
  146. Paul M. Ridker
  147. Harriëtte Riese
  148. Samuli Ripatti
  149. Jerome I. Rotter
  150. Igor Rudan
  151. Yasaman Saba
  152. Aude Saint Pierre
  153. Cinzia F. Sala
  154. Antti-Pekka Sarin
  155. Reinhold Schmidt
  156. Rodney Scott
  157. Marc A. Seelen
  158. Denis C. Shields
  159. David Siscovick
  160. Rossella Sorice
  161. Alice Stanton
  162. David J. Stott
  163. Johan Sundström
  164. Morris Swertz
  165. Kent D. Taylor
  166. Simon Thom
  167. Ioanna Tzoulaki
  168. Christophe Tzourio
  169. André G. Uitterlinden
  170. Uwe Vöker
  171. Peter Vollenweider
  172. Sarah Wild
  173. Gonneke Willemsen
  174. Alan F. Wright
  175. Jie Yao
  176. Sébastien Thériault
  177. David Conen
  178. John Attia
  179. Peter Sever
  180. Stéphanie Debette
  181. Dennis O. Mook-Kanamori
  182. Eleftheria Zeggini
  183. Tim D. Spector
  184. Pim van der Harst
  185. Colin N. A. Palmer
  186. Anne-Claire Vergnaud
  187. Ruth J. F. Loos
  188. Ozren Polasek
  189. John M. Starr
  190. Giorgia Girotto
  191. Caroline Hayward
  192. Jaspal S. Kooner
  193. Cecilia M. Lindgren
  194. Veronique Vitart
  195. Nilesh J. Samani
  196. Jaakko Tuomilehto
  197. Ulf Gyllensten
  198. Paul Knekt
  199. Ian J. Deary
  200. Marina Ciullo
  201. Roberto Elosua
  202. Bernard D. Keavney
  203. Andrew A. Hicks
  204. Robert A. Scott
  205. Paolo Gasparini
  206. Maris Laan
  207. Yongmei Liu
  208. Hugh Watkins
  209. Catharina A. Hartman
  210. Veikko Salomaa
  211. Daniela Toniolo
  212. Markus Perola
  213. James F. Wilson
  214. Helena Schmidt
  215. Jing Hua Zhao
  216. Terho Lehtimäki
  217. Cornelia M. van Duijn
  218. Vilmundur Gudnason
  219. Bruce M. Psaty
  220. Annette Peters
  221. Rainer Rettig
  222. Alan James
  223. J. Wouter Jukema
  224. David P. Strachan
  225. Walter Palmas
  226. Andres Metspalu
  227. Erik Ingelsson
  228. Dorret I. Boomsma
  229. Oscar H. Franco
  230. Murielle Bochud
  231. Christopher Newton-Cheh
  232. Patricia B. Munroe
  233. Paul Elliott
  234. Daniel I. Chasman
  235. Aravinda Chakravarti
  236. Joanne Knight
  237. Andrew P. Morris
  238. Daniel Levy
  239. Martin D. Tobin
  240. Harold Snieder
  241. Mark J. Caulfield
  242. Georg B. Ehret

Publication date

February 22, 2017

Summary:

Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150,134 European ancestry individuals and sought significant evidence for independent replication in a further 228,245 individuals. We report 6 new signals of association in or near HSPB7, TNXB, LRP12, LOC283335, SEPT9 and AKT2, and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA. Combining large whole-blood gene expression resources totaling 12,607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in BP regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation.

Published in

bioRxiv

DOI

http://dx.doi.org/10.1101/110833

Subjects


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  • Novel blood pressure locus and gene discovery using Genome-Wide Association Study and expression data sets from blood and the kidney

    Louise Wain, Ahmad Vaez, Rick Jansen, Roby Joehanes, Peter J. van der Most, A. Mesut Erzurumluoglu, Paul O'Reilly, Claudia P. Cabrera, Helen R. Warren, Lynda M. Rose, Germaine C. Verwoert, Jouke-Jan Hottenga, Rona J. Strawbridge, Tonu Esko, Dan E. Arking, Shih-Jen Hwang, Xiuqing Guo, Zoltán Kutalik, Stella Trompet, Nick Shrine, Alexander Teumer, Janina S. Ried, Joshua C. Bis, Albert V. Smith, Najaf Amin, Ilja M. Nolte, Leo-Pekka Lyytikainen, Anubha Mahajan, Nicholas J. Wareham, Edith Hofer, Peter K. Joshi, Kati Kristiansson, Michela Traglia, Aki S. Havulinna, Anuj Goel, Mike A. Nalls, Siim Sõber, Dragana Vuckovic, Jian'an Luan, Fabiola Del Greco M, Kristin L. Ayers, Jaume Marrugat, Daniela Ruggiero, Lorna M. Lopez, Teemu Niiranen, Stefan Enroth, Anne U. Jackson, Christopher P. Nelson, Jennifer E. Huffman, Weihua Zhang, Jonathan Marten, Ilaria Gandin, Sarah E. Harris, Tatijana Zemonik, Yingchang Lu, Evangelos Evangelou, Nabi Shah, Martin H. de Borst, Massimo Mangino, Bram P. Prins, Archie Campbell, Ruifang Li-Gao, Ganesh Chauhan, Christopher Oldmeadow, Goncalo Abecasis, Maryam Abedi, Caterina M. Barbieri, Michael R. Barnes, Chiara Batini, John Beilby, Tineka Blake, Michael Boehnke, Erwin P. Bottinger, Peter S. Braund, Morris Brown, Marco Brumat, Harry Campbell, John C. Chambers, Massimiliano Cocca, Francis Collins, John Connell, Heather J. Cordell, Jeffrey J. Damman, Gail Davies, Eco J. de Geus, Renée de Mutsert, Joris Deelen, Yusuf Demirkale, Alex S. F. Doney, Marcus Dörr, Martin Farrall, Teresa Ferreira, Mattias Frånberg, He Gao, Vilmantas Giedraitis, Christian Gieger, Franco Giulianini, Alan J. Gow, Anders Hamsten, Tamara B. Harris, Albert Hofman, Elizabeth G. Holliday, Jennie Hui, Marjo-Riitta Jarvelin, Åsa Johansson, Andrew D. Johnson, Pekka Jousilahti, Antti Jula, Mika Kähönen, Sekar Kathiresan, Kay-Tee Khaw, Ivana Kolcic, Seppo Koskinen, Claudia Langenberg, Marty Larson, Lenore J. Launer, Benjamin Lehne, David C. M. Liewald, Li Lin, Lars Lind, François Mach, Chrysovalanto Mamasoula, Cristina Menni, Borbala Mifsud, Yuri Milaneschi, Anna Morgan, Andrew D. Morris, Alanna C. Morrison, Peter J. Munson, Priyanka Nandakumar, Quang Tri Nguyen, Teresa Nutile, Albertine J. Oldehinkel, Ben A. Oostra, Elin Org, Sandosh Padmanabhan, Aarno Palotie, Guillaume Pare, Alison Pattie, Brenda W. J. H. Penninx, Neil Poulter, Peter P. Pramstaller, Olli T. Raitakari, Meixia Ren, Kenneth Rice, Paul M. Ridker, Harriëtte Riese, Samuli Ripatti, Jerome I. Rotter, Igor Rudan, Yasaman Saba, Aude Saint Pierre, Cinzia F. Sala, Antti-Pekka Sarin, Reinhold Schmidt, Rodney Scott, Marc A. Seelen, Denis C. Shields, David Siscovick, Rossella Sorice, Alice Stanton, David J. Stott, Johan Sundström, Morris Swertz, Kent D. Taylor, Simon Thom, Ioanna Tzoulaki, Christophe Tzourio, André G. Uitterlinden, Uwe Vöker, Peter Vollenweider, Sarah Wild, Gonneke Willemsen, Alan F. Wright, Jie Yao, Sébastien Thériault, David Conen, John Attia, Peter Sever, Stéphanie Debette, Dennis O. Mook-Kanamori, Eleftheria Zeggini, Tim D. Spector, Pim van der Harst, Colin N. A. Palmer, Anne-Claire Vergnaud, Ruth J. F. Loos, Ozren Polasek, John M. Starr, Giorgia Girotto, Caroline Hayward, Jaspal S. Kooner, Cecilia M. Lindgren, Veronique Vitart, Nilesh J. Samani, Jaakko Tuomilehto, Ulf Gyllensten, Paul Knekt, Ian J. Deary, Marina Ciullo, Roberto Elosua, Bernard D. Keavney, Andrew A. Hicks, Robert A. Scott, Paolo Gasparini, Maris Laan, Yongmei Liu, Hugh Watkins, Catharina A. Hartman, Veikko Salomaa, Daniela Toniolo, Markus Perola, James F. Wilson, Helena Schmidt, Jing Hua Zhao, Terho Lehtimäki, Cornelia M. van Duijn, Vilmundur Gudnason, Bruce M. Psaty, Annette Peters, Rainer Rettig, Alan James, J. Wouter Jukema, David P. Strachan, Walter Palmas, Andres Metspalu, Erik Ingelsson, Dorret I. Boomsma, Oscar H. Franco, Murielle Bochud, Christopher Newton-Cheh, Patricia B. Munroe, Paul Elliott, Daniel I. Chasman, Aravinda Chakravarti, Joanne Knight, Andrew P. Morris, Daniel Levy, Martin D. Tobin, Harold Snieder, Mark J. Caulfield, Georg B. Ehret,

    Journal Article - 20170915

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