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

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.

SUBMITTER: Kottgen A 

PROVIDER: S-EPMC3663712 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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

Köttgen Anna A   Albrecht Eva E   Teumer Alexander A   Vitart Veronique V   Krumsiek Jan J   Hundertmark Claudia C   Pistis Giorgio G   Ruggiero Daniela D   O'Seaghdha Conall M CM   Haller Toomas T   Yang Qiong Q   Tanaka Toshiko T   Johnson Andrew D AD   Kutalik Zoltán Z   Smith Albert V AV   Shi Julia J   Struchalin Maksim M   Middelberg Rita P S RP   Brown Morris J MJ   Gaffo Angelo L AL   Pirastu Nicola N   Li Guo G   Hayward Caroline C   Zemunik Tatijana T   Huffman Jennifer J   Yengo Loic L   Zhao Jing Hua JH   Demirkan Ayse A   Feitosa Mary F MF   Liu Xuan X   Malerba Giovanni G   Lopez Lorna M LM   van der Harst Pim P   Li Xinzhong X   Kleber Marcus E ME   Hicks Andrew A AA   Nolte Ilja M IM   Johansson Asa A   Murgia Federico F   Wild Sarah H SH   Bakker Stephan J L SJ   Peden John F JF   Dehghan Abbas A   Steri Maristella M   Tenesa Albert A   Lagou Vasiliki V   Salo Perttu P   Mangino Massimo M   Rose Lynda M LM   Lehtimäki Terho T   Woodward Owen M OM   Okada Yukinori Y   Tin Adrienne A   Müller Christian C   Oldmeadow Christopher C   Putku Margus M   Czamara Darina D   Kraft Peter P   Frogheri Laura L   Thun Gian Andri GA   Grotevendt Anne A   Gislason Gauti Kjartan GK   Harris Tamara B TB   Launer Lenore J LJ   McArdle Patrick P   Shuldiner Alan R AR   Boerwinkle Eric E   Coresh Josef J   Schmidt Helena H   Schallert Michael M   Martin Nicholas G NG   Montgomery Grant W GW   Kubo Michiaki M   Nakamura Yusuke Y   Tanaka Toshihiro T   Munroe Patricia B PB   Samani Nilesh J NJ   Jacobs David R DR   Liu Kiang K   D'Adamo Pio P   Ulivi Sheila S   Rotter Jerome I JI   Psaty Bruce M BM   Vollenweider Peter P   Waeber Gerard G   Campbell Susan S   Devuyst Olivier O   Navarro Pau P   Kolcic Ivana I   Hastie Nicholas N   Balkau Beverley B   Froguel Philippe P   Esko Tõnu T   Salumets Andres A   Khaw Kay Tee KT   Langenberg Claudia C   Wareham Nicholas J NJ   Isaacs Aaron A   Kraja Aldi A   Zhang Qunyuan Q   Wild Philipp S PS   Scott Rodney J RJ   Holliday Elizabeth G EG   Org Elin E   Org Elin E   Viigimaa Margus M   Bandinelli Stefania S   Metter Jeffrey E JE   Lupo Antonio A   Trabetti Elisabetta E   Sorice Rossella R   Döring Angela A   Lattka Eva E   Strauch Konstantin K   Theis Fabian F   Waldenberger Melanie M   Wichmann H-Erich HE   Davies Gail G   Gow Alan J AJ   Bruinenberg Marcel M   Stolk Ronald P RP   Kooner Jaspal S JS   Zhang Weihua W   Winkelmann Bernhard R BR   Boehm Bernhard O BO   Lucae Susanne S   Penninx Brenda W BW   Smit Johannes H JH   Curhan Gary G   Mudgal Poorva P   Plenge Robert M RM   Portas Laura L   Persico Ivana I   Kirin Mirna M   Wilson James F JF   Mateo Leach Irene I   van Gilst Wiek H WH   Goel Anuj A   Ongen Halit H   Hofman Albert A   Rivadeneira Fernando F   Uitterlinden Andre G AG   Imboden Medea M   von Eckardstein Arnold A   Cucca Francesco F   Nagaraja Ramaiah R   Piras Maria Grazia MG   Nauck Matthias M   Schurmann Claudia C   Budde Kathrin K   Ernst Florian F   Farrington Susan M SM   Theodoratou Evropi E   Prokopenko Inga I   Stumvoll Michael M   Jula Antti A   Perola Markus M   Salomaa Veikko V   Shin So-Youn SY   Spector Tim D TD   Sala Cinzia C   Ridker Paul M PM   Kähönen Mika M   Viikari Jorma J   Hengstenberg Christian C   Nelson Christopher P CP   Meschia James F JF   Nalls Michael A MA   Sharma Pankaj P   Singleton Andrew B AB   Kamatani Naoyuki N   Zeller Tanja T   Burnier Michel M   Attia John J   Laan Maris M   Klopp Norman N   Hillege Hans L HL   Kloiber Stefan S   Choi Hyon H   Pirastu Mario M   Tore Silvia S   Probst-Hensch Nicole M NM   Völzke Henry H   Gudnason Vilmundur V   Parsa Afshin A   Schmidt Reinhold R   Whitfield John B JB   Fornage Myriam M   Gasparini Paolo P   Siscovick David S DS   Polašek Ozren O   Campbell Harry H   Rudan Igor I   Bouatia-Naji Nabila N   Metspalu Andres A   Loos Ruth J F RJ   van Duijn Cornelia M CM   Borecki Ingrid B IB   Ferrucci Luigi L   Gambaro Giovanni G   Deary Ian J IJ   Wolffenbuttel Bruce H R BH   Chambers John C JC   März Winfried W   Pramstaller Peter P PP   Snieder Harold H   Gyllensten Ulf U   Wright Alan F AF   Navis Gerjan G   Watkins Hugh H   Witteman Jacqueline C M JC   Sanna Serena S   Schipf Sabine S   Dunlop Malcolm G MG   Tönjes Anke A   Ripatti Samuli S   Soranzo Nicole N   Toniolo Daniela D   Chasman Daniel I DI   Raitakari Olli O   Kao W H Linda WH   Ciullo Marina M   Fox Caroline S CS   Caulfield Mark M   Bochud Murielle M   Gieger Christian C  

Nature genetics 20121223 2

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). Associati  ...[more]

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