Plate IV.572 · Publications

Genome-wide association analyses identify 18 new loci associated with serum urate concentrations

Article in Nature Genetics, 23 December 2012.

Open accessResearch area: Metabolite, Association, Metabolomics Data

Authors

  1. LifeLines Cohort Study
  2. Anna Köttgen
  3. CARDIoGRAM Consortium
  4. DIAGRAM Consortium
  5. ICBP Consortium
  6. MAGIC Consortium
  7. Eva Albrecht
  8. Alexander Teumer
  9. Veronique Vitart
  10. Jan Krumsiek
  11. Claudia Hundertmark
  12. Giorgio Pistis
  13. Daniela Ruggiero
  14. Conall M O'Seaghdha
  15. Toomas Haller
  16. Qiong Yang
  17. Toshiko Tanaka
  18. Andrew D Johnson
  19. Zoltán Kutalik
  20. Albert V Smith
  21. Julia Shi
  22. Maksim Struchalin
  23. Rita P S Middelberg
  24. Morris J Brown
  25. Angelo L Gaffo
  26. Nicola Pirastu
  27. Guo Li
  28. Caroline Hayward
  29. Tatijana Zemunik
  30. Jennifer Huffman
  31. Loic Yengo
  32. Jing Hua Zhao
  33. Ayse Demirkan
  34. Mary F Feitosa
  35. Xuan Liu
  36. Giovanni Malerba
  37. Lorna M Lopez
  38. Pim van der Harst
  39. Xinzhong Li
  40. Marcus E Kleber
  41. Andrew A Hicks
  42. Ilja M Nolte
  43. Asa Johansson
  44. Federico Murgia
  45. Sarah H Wild
  46. Stephan J L Bakker
  47. John F Peden
  48. Abbas Dehghan
  49. Maristella Steri
  50. Albert Tenesa
  51. Vasiliki Lagou
  52. Perttu Salo
  53. Massimo Mangino
  54. Lynda M Rose
  55. Terho Lehtimäki
  56. Owen M Woodward
  57. Yukinori Okada
  58. Adrienne Tin
  59. Christian Müller
  60. Christopher Oldmeadow
  61. Margus Putku
  62. Darina Czamara
  63. Peter Kraft
  64. Laura Frogheri
  65. Gian Andri Thun
  66. Anne Grotevendt
  67. Gauti Kjartan Gislason
  68. Tamara B Harris
  69. Lenore J Launer
  70. Patrick McArdle
  71. Alan R Shuldiner
  72. Eric Boerwinkle
  73. Josef Coresh
  74. Helena Schmidt
  75. Michael Schallert
  76. Nicholas G Martin
  77. Grant W Montgomery
  78. Michiaki Kubo
  79. Yusuke Nakamura
  80. Toshihiro Tanaka
  81. Patricia B Munroe
  82. Nilesh J Samani
  83. David R Jacobs
  84. Kiang Liu
  85. Pio D'Adamo
  86. Sheila Ulivi
  87. Jerome I Rotter
  88. Bruce M Psaty
  89. Peter Vollenweider
  90. Gerard Waeber
  91. Susan Campbell
  92. Olivier Devuyst
  93. Pau Navarro
  94. Ivana Kolcic
  95. Nicholas Hastie
  96. Beverley Balkau
  97. Philippe Froguel
  98. Tõnu Esko
  99. Andres Salumets
  100. Kay Tee Khaw
  101. Claudia Langenberg
  102. Nicholas J Wareham
  103. Aaron Isaacs
  104. Aldi Kraja
  105. Qunyuan Zhang
  106. Philipp S Wild
  107. Rodney J Scott
  108. Elizabeth G Holliday
  109. Elin Org
  110. Margus Viigimaa
  111. Stefania Bandinelli
  112. Jeffrey E Metter
  113. Antonio Lupo
  114. Elisabetta Trabetti
  115. Rossella Sorice
  116. Angela Döring
  117. Eva Lattka
  118. Konstantin Strauch
  119. Fabian Theis
  120. Melanie Waldenberger
  121. H-Erich Wichmann
  122. Gail Davies
  123. Alan J Gow
  124. Marcel Bruinenberg
  125. Ronald P Stolk
  126. Jaspal S Kooner
  127. Weihua Zhang
  128. Bernhard R Winkelmann
  129. Bernhard O Boehm
  130. Susanne Lucae
  131. Brenda W Penninx
  132. Johannes H Smit
  133. Gary Curhan
  134. Poorva Mudgal
  135. Robert M Plenge
  136. Laura Portas
  137. Ivana Persico
  138. Mirna Kirin
  139. James F Wilson
  140. Irene Mateo Leach
  141. Wiek H van Gilst
  142. Anuj Goel
  143. Halit Ongen
  144. Albert Hofman
  145. Fernando Rivadeneira
  146. Andre G Uitterlinden
  147. Medea Imboden
  148. Arnold von Eckardstein
  149. Francesco Cucca
  150. Ramaiah Nagaraja
  151. Maria Grazia Piras
  152. Matthias Nauck
  153. Claudia Schurmann
  154. Kathrin Budde
  155. Florian Ernst
  156. Susan M Farrington
  157. Evropi Theodoratou
  158. Inga Prokopenko
  159. Michael Stumvoll
  160. Antti Jula
  161. Markus Perola
  162. Veikko Salomaa
  163. So-Youn Shin
  164. Tim D Spector
  165. Cinzia Sala
  166. Paul M Ridker
  167. Mika Kähönen
  168. Jorma Viikari
  169. Christian Hengstenberg
  170. Christopher P Nelson
  171. James F Meschia
  172. Michael A Nalls
  173. Pankaj Sharma
  174. Andrew B Singleton
  175. Naoyuki Kamatani
  176. Tanja Zeller
  177. Michel Burnier
  178. John Attia
  179. Maris Laan
  180. Norman Klopp
  181. Hans L Hillege
  182. Stefan Kloiber
  183. Hyon Choi
  184. Mario Pirastu
  185. Silvia Tore
  186. Nicole M Probst-Hensch
  187. Henry Völzke
  188. Vilmundur Gudnason
  189. Afshin Parsa
  190. Reinhold Schmidt
  191. John B Whitfield
  192. Myriam Fornage
  193. Paolo Gasparini
  194. David S Siscovick
  195. Ozren Polašek
  196. Harry Campbell
  197. Igor Rudan
  198. Nabila Bouatia-Naji
  199. Andres Metspalu
  200. Ruth J F Loos
  201. Cornelia M van Duijn
  202. Ingrid B Borecki
  203. Luigi Ferrucci
  204. Giovanni Gambaro
  205. Ian J Deary
  206. Bruce H R Wolffenbuttel
  207. John C Chambers
  208. Winfried März
  209. Peter P Pramstaller
  210. Harold Snieder
  211. Ulf Gyllensten
  212. Alan F Wright
  213. Gerjan Navis
  214. Hugh Watkins
  215. Jacqueline C M Witteman
  216. Serena Sanna
  217. Sabine Schipf
  218. Malcolm G Dunlop
  219. Anke Tönjes
  220. Samuli Ripatti
  221. Nicole Soranzo
  222. Daniela Toniolo
  223. Daniel I Chasman
  224. Olli Raitakari
  225. W H Linda Kao
  226. Marina Ciullo
  227. Caroline S Fox
  228. Mark Caulfield
  229. Murielle Bochud
  230. Christian Gieger

Abstract

Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SFMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional excretion of urate. Network analyses implicate the inhibins-activins signaling pathways and glucose metabolism in systemic urate control. New candidate genes for serum urate concentration highlight the importance of metabolic control of urate production and excretion, which may have implications for the treatment and prevention of gout.

Cite

@article{study2012genome,
  title = {{Genome-wide association analyses identify 18 new loci associated with serum urate concentrations}},
  author = {LifeLines Cohort Study and Köttgen, Anna and CARDIoGRAM Consortium and DIAGRAM Consortium and ICBP Consortium and MAGIC Consortium and Albrecht, Eva and Teumer, Alexander and Vitart, Veronique and Krumsiek, Jan and Hundertmark, Claudia and Pistis, Giorgio and Ruggiero, Daniela and O'Seaghdha, Conall M and Haller, Toomas and Yang, Qiong and Tanaka, Toshiko and Johnson, Andrew D and Kutalik, Zoltán and Smith, Albert V and Shi, Julia and Struchalin, Maksim and Middelberg, Rita P S and Brown, Morris J and Gaffo, Angelo L and Pirastu, Nicola and Li, Guo and Hayward, Caroline and Zemunik, Tatijana and Huffman, Jennifer and Yengo, Loic and Zhao, Jing Hua and Demirkan, Ayse and Feitosa, Mary F and Liu, Xuan and Malerba, Giovanni and Lopez, Lorna M and van der Harst, Pim and Li, Xinzhong and Kleber, Marcus E and Hicks, Andrew A and Nolte, Ilja M and Johansson, Asa and Murgia, Federico and Wild, Sarah H and Bakker, Stephan J L and Peden, John F and Dehghan, Abbas and Steri, Maristella and Tenesa, Albert and Lagou, Vasiliki and Salo, Perttu and Mangino, Massimo and Rose, Lynda M and Lehtimäki, Terho and Woodward, Owen M and Okada, Yukinori and Tin, Adrienne and Müller, Christian and Oldmeadow, Christopher and Putku, Margus and Czamara, Darina and Kraft, Peter and Frogheri, Laura and Thun, Gian Andri and Grotevendt, Anne and Gislason, Gauti Kjartan and Harris, Tamara B and Launer, Lenore J and McArdle, Patrick and Shuldiner, Alan R and Boerwinkle, Eric and Coresh, Josef and Schmidt, Helena and Schallert, Michael and Martin, Nicholas G and Montgomery, Grant W and Kubo, Michiaki and Nakamura, Yusuke and Tanaka, Toshihiro and Munroe, Patricia B and Samani, Nilesh J and Jacobs, David R and Liu, Kiang and D'Adamo, Pio and Ulivi, Sheila and Rotter, Jerome I and Psaty, Bruce M and Vollenweider, Peter and Waeber, Gerard and Campbell, Susan and Devuyst, Olivier and Navarro, Pau and Kolcic, Ivana and Hastie, Nicholas and Balkau, Beverley and Froguel, Philippe and Esko, Tõnu and Salumets, Andres and Khaw, Kay Tee and Langenberg, Claudia and Wareham, Nicholas J and Isaacs, Aaron and Kraja, Aldi and Zhang, Qunyuan and Wild, Philipp S and Scott, Rodney J and Holliday, Elizabeth G and Org, Elin and Viigimaa, Margus and Bandinelli, Stefania and Metter, Jeffrey E and Lupo, Antonio and Trabetti, Elisabetta and Sorice, Rossella and Döring, Angela and Lattka, Eva and Strauch, Konstantin and Theis, Fabian and Waldenberger, Melanie and Wichmann, H-Erich and Davies, Gail and Gow, Alan J and Bruinenberg, Marcel and Stolk, Ronald P and Kooner, Jaspal S and Zhang, Weihua and Winkelmann, Bernhard R and Boehm, Bernhard O and Lucae, Susanne and Penninx, Brenda W and Smit, Johannes H and Curhan, Gary and Mudgal, Poorva and Plenge, Robert M and Portas, Laura and Persico, Ivana and Kirin, Mirna and Wilson, James F and Leach, Irene Mateo and van Gilst, Wiek H and Goel, Anuj and Ongen, Halit and Hofman, Albert and Rivadeneira, Fernando and Uitterlinden, Andre G and Imboden, Medea and von Eckardstein, Arnold and Cucca, Francesco and Nagaraja, Ramaiah and Piras, Maria Grazia and Nauck, Matthias and Schurmann, Claudia and Budde, Kathrin and Ernst, Florian and Farrington, Susan M and Theodoratou, Evropi and Prokopenko, Inga and Stumvoll, Michael and Jula, Antti and Perola, Markus and Salomaa, Veikko and Shin, So-Youn and Spector, Tim D and Sala, Cinzia and Ridker, Paul M and Kähönen, Mika and Viikari, Jorma and Hengstenberg, Christian and Nelson, Christopher P and Meschia, James F and Nalls, Michael A and Sharma, Pankaj and Singleton, Andrew B and Kamatani, Naoyuki and Zeller, Tanja and Burnier, Michel and Attia, John and Laan, Maris and Klopp, Norman and Hillege, Hans L and Kloiber, Stefan and Choi, Hyon and Pirastu, Mario and Tore, Silvia and Probst-Hensch, Nicole M and Völzke, Henry and Gudnason, Vilmundur and Parsa, Afshin and Schmidt, Reinhold and Whitfield, John B and Fornage, Myriam and Gasparini, Paolo and Siscovick, David S and Polašek, Ozren and Campbell, Harry and Rudan, Igor and Bouatia-Naji, Nabila and Metspalu, Andres and Loos, Ruth J F and van Duijn, Cornelia M and Borecki, Ingrid B and Ferrucci, Luigi and Gambaro, Giovanni and Deary, Ian J and Wolffenbuttel, Bruce H R and Chambers, John C and März, Winfried and Pramstaller, Peter P and Snieder, Harold and Gyllensten, Ulf and Wright, Alan F and Navis, Gerjan and Watkins, Hugh and Witteman, Jacqueline C M and Sanna, Serena and Schipf, Sabine and Dunlop, Malcolm G and Tönjes, Anke and Ripatti, Samuli and Soranzo, Nicole and Toniolo, Daniela and Chasman, Daniel I and Raitakari, Olli and Kao, W H Linda and Ciullo, Marina and Fox, Caroline S and Caulfield, Mark and Bochud, Murielle and Gieger, Christian},
  journal = {Nature Genetics},
  publisher = {Springer Science and Business Media LLC},
  year = {2012},
  month = dec,
  doi = {10.1038/ng.2500},
  url = {https://doi.org/10.1038/ng.2500},
  pmid = {23263486},
  pmcid = {PMC3663712}
}
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