• DOI:10.1038/ng.2500
• Corpus ID: 205346471

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

@article{Kttgen2012GenomewideAA,
  title={Genome-wide association analyses identify 18 new loci associated with serum urate concentrations},
  author={Anna K{\"o}ttgen and Eva Albrecht and Alexander Teumer and Veronique Vitart and Jan Krumsiek and Claudia Hundertmark and Giorgio Pistis and Daniela Ruggiero and Conall M. O’Seaghdha and Toomas Haller and Qiong Yang and Toshiko Tanaka and Andrew D. Johnson and Zolt{\'a}n Kutalik and Albert Vernon Smith and Julia Zhuo Shi and Maksim V. Struchalin and Rita P. S. Middelberg and Morris J. Brown and Angelo L. Gaffo and Nicola Pirastu and Guo Li and Caroline Hayward and Tatijana Zemunik and Jennifer E. Huffman and Loic Yengo and Jing Hua Zhao and Ayşe Demirkan and Mary F. Feitosa and Xuan Liu and Giovanni Malerba and Lorna M. Lopez and Pim van der Harst and Xinzhong Li and Marcus Edi Kleber and Andrew A. Hicks and Ilja Maria Nolte and {\AA}sa Johansson and Federico Murgia and Sarah H. Wild and Stephan J. L. Bakker and John F. Peden and Abbas Dehghan and Maristella Steri and Albert Tenesa and Vasiliki Lagou and Perttu P. Salo and Massimo Mangino and Lynda M Rose and Terho Lehtim{\"a}ki and Owen M. Woodward and Yukinori Okada and Adrienne Tin and Christian M{\"u}ller and Christopher Oldmeadow and Margus Putku and Darina Czamara and Peter Kraft and Laura Frogheri and Gian Andri Thun and Anne Grotevendt and Gauti Kjartan G{\'i}slason and Tamara B. Harris and Lenore J. Launer and Patrick F. McArdle and Alan R. Shuldiner and Eric Boerwinkle and Josef Coresh and Helena Schmidt and Michael Schallert and Nicholas G. Martin and Grant W. Montgomery and Michiaki Kubo and Yusuke Nakamura and Toshihiro Tanaka and Patricia B. Munroe and Nilesh J. Samani and David R. Jacobs and Kiang Liu and Pio D'Adamo and Sheila Ulivi and Jerome I. Rotter and Bruce M. Psaty and Peter Vollenweider and G{\'e}rard Waeber and Susan Campbell and Olivier Devuyst and Pau Navarro and Ivana Kol{\vc}i{\'c} and Nicholas D. Hastie and Beverley Balkau and Philippe Froguel and T{\~o}nu Esko and Andres Salumets and Kay-Tee Khaw and Claudia Langenberg and Nicholas J. Wareham and Aaron Isaacs and Aldi T. Kraja and Qunyuan Zhang and Philipp S. Wild and Rodney J. Scott and Elizabeth G. Holliday and Elin Org and Margus Viigimaa and Stefania Bandinelli and Jeffrey E. Metter and Antonio Lupo and Elisabetta Trabetti and Rossella Sorice and Angela D{\"o}ring and Eva Lattka and Konstantin Strauch and Fabian J Theis and Melanie Waldenberger and Heinz-Erich Wichmann and Gail Davies and Alan J. Gow and Marcel Bruinenberg and Ronald P Stolk and Jaspal S. Kooner and Weihua Zhang and Bernhard R. Winkelmann and Bernhard Otto Boehm and Susanne Lucae and Brenda W.J.H. Penninx and Johannes H. Smit and Gary C Curhan and Poorva Mudgal and Robert M. Plenge and Laura Portas and Ivana Persico and Mirna Abaffy Kirin and James F. Wilson and Irene Mateo Leach and Wiek H. van Gilst and Anuj Goel and Halit Ongen and Albert Hofman and Fernando Rivadeneira and Andr{\'e} G. Uitterlinden and Medea Imboden and Arnold von Eckardstein and Francesco Cucca and Ramaiah Nagaraja and Maria Grazia Piras and Matthias Nauck and Claudia Schurmann and Kathrin Budde and Florian D. Ernst and Susan M. Farrington and Evropi Theodoratou and Inga Prokopenko and Michael Stumvoll and Antti M. Jula and Markus Perola and Veikko V Salomaa and So-Youn Shin and Tim D. Spector and Cinzia Felicita Sala and Paul M. Ridker and Mika K{\"a}h{\"o}nen and Jorma S.A. Viikari and Christian Hengstenberg and Christopher P. Nelson and James F. Meschia and Mike A. Nalls and Pankaj Sharma and Andrew B. Singleton and Naoyuki Kamatani and Tanja Zeller and Michel Burnier and John Richard Attia and Maris Laan and Norman Klopp and Hans L. Hillege and Stefan Kloiber and Hyon K. Choi and Mario Pirastu and Silvia Tore and Nicole Probst-Hensch and Henry V{\"o}lzke and Vilmundur G. Gudnason and Afshin Parsa and Reinhold Schmidt and John B. Whitfield and Myriam Fornage and Paolo Gasparini and David S. Siscovick and Ozren Pola{\vs}ek and Harry Campbell and Igor Rudan and Nabila Bouatia-Naji and Andres Metspalu and Ruth J. F. Loos and Cornelia van Duijn and Ingrid B. Borecki and Luigi Ferrucci and Giovanni Gambaro and Ian J. Deary and Bruce H. R. Wolffenbuttel and John C. Chambers and Winfried M{\"a}rz and Peter Paul Pramstaller and Harold Snieder and Ulf Gyllensten and Alan F. Wright and Gerjan J Navis and Hugh C. Watkins and Jacqueline C. M. Witteman and Serena Sanna and Sabine Schipf and Malcolm G. Dunlop and Anke Tönjes and Samuli Ripatti and Nicole Soranzo and Daniela Toniolo and Daniel I. Chasman and Olli T. Raitakari and Wen Kao and Marina Ciullo and Caroline S. Fox and Mark J. Caulfield and Murielle Bochud and Christian Gieger},
  journal={Nature Genetics},
  year={2012},
  volume={45},
  pages={145-154}
}

• A. Köttgen, E. Albrecht, +222 authors C. Gieger
• Published 23 December 2012
• Biology
• Nature Genetics

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.