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

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

Nat Genet 2013 Feb 23;45(2):145-54. Epub 2012 Dec 23.

Renal Division, Freiburg University Hospital, Freiburg, Germany.

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.

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http://dx.doi.org/10.1038/ng.2500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3663712PMC
February 2013
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References

(Supplied by CrossRef)

A So et al.
J. Clin. Invest. 2010

Y Zhu et al.
Arthritis Rheum. 2011

E Arromdee et al.
J. Rheumatol. 2002

KL Wallace et al.
J. Rheumatol. 2004

HG Yoo et al.
Rheumatol. Int. 2011

JA Singh et al.
Curr. Rheumatol. Rep. 2009

MA Becker et al.
J. Rheumatol. 2009

RA Brook et al.
Curr. Med. Res. Opin. 2006

MA Hediger et al.
Physiology (Bethesda) 2005

JB Whitfield et al.
Acta Genet. Med. Gemellol. (Roma) 1983

Q Yang et al.
Metabolism 2005

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