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DOI: 10.1038/ng.2500
¤ OpenAccess: Green
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Genome-wide association analyses identify 18 new loci associated with serum urate concentrations
Anna Köttgen,Eva Albrecht,Alexander Teumer,Véronique Vitart,Jan Krumsiek,Claudia Hundertmark,Giorgio Pistis,Daniela Ruggiero,Conall M. O’Seaghdha,Toomas Haller,Qiong Yang,Toshiko Tanaka,Andrew D. Johnson,Zoltán Kutalik,Albert V. Smith,Julia Shi,Maksim Struchalin,Rita P. S. Middelberg,Morris J. Brown,Angelo Gaffo,Nicola Pirastu,Li Guo,Caroline Hayward,Tatijana Zemunik,Jennifer E. Huffman,Loïc Yengo,Jing Hua Zhao,Ayşe Demirkan,Mary F. Feitosa,Xuan Li,Giovanni Malerba,Lorna M. Lopez,Pim van der Harst,Xinzhong Li,Marcus E. Kleber,Andrew A. Hicks,Ilja M. Nolte,Åsa 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 Gíslason,Tamara B. Harris,Lenore J. Launer,Patrick F. 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,Péter Vollenweider,Gérard Waeber,Susan Campbell,Olivier Devuyst,Pau Navarro,Ivana Kolčić,Nicholas D. Hastie,Beverley Balkau,Philippe Froguel,Tõnu Esko,Andres Salumets,Kay Tee Khaw,Claudia Langenberg,Nicholas J. Wareham,Aaron Isaacs,Aldi T. Kraja,Qunyuan Zhang,Philipp S. Wild,Rodney J. Scott,Elizabeth G. Holliday,Elin Org,Margus Viigimaa,Stefania Bandinelli,Jeffrey Metter,Antonio Lupo,Elisabetta Trabetti,Rossella Sorice,Angela Döring,Eva Lattka,Konstantin Strauch,Fabian J. Theis,Mélanie Waldenberger,Heinz‐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. J. H. Penninx,Johannes H. Smit,Gary C. 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,André 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 Τheodoratou,Inga Prokopenko,Michael Stümvoll,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 Singleton,Naoyuki Kamatani,Tanja Zeller,Michel Burnier,John Attia,Maris Laan,Norman Klopp,Hans L. Hillege,Stefan Kloiber,Hyon K. Choi,Mario Pirastu,Silvia Tore,Nicole 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 T. Raitakari,W. H. Linda Kao,Marina Ciullo,Caroline S. Fox,Mark J. Caulfield,Murielle Bochud,Christian Gieger
Biology
Genome-wide association study
Genetics
2012
Anna Köttgen and colleagues report genome-wide association studies for serum urate in over 140,000 individuals from the Global Urate Genetics Consortium (GUGC). They identify 18 loci newly associated with serum urate concentrations and confirm 10 known loci, characterize their associations with gout and include a network analysis suggesting a role for inhibins-activins pathways in regulating urate homeostasis. 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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“Genome-wide association analyses identify 18 new loci associated with serum urate concentrations” is a paper by Anna Köttgen Eva Albrecht Alexander Teumer Véronique Vitart Jan Krumsiek Claudia Hundertmark Giorgio Pistis Daniela Ruggiero Conall M. O’Seaghdha Toomas Haller Qiong Yang Toshiko Tanaka Andrew D. Johnson Zoltán Kutalik Albert V. Smith Julia Shi Maksim Struchalin Rita P. S. Middelberg Morris J. Brown Angelo Gaffo Nicola Pirastu Li Guo Caroline Hayward Tatijana Zemunik Jennifer E. Huffman Loïc Yengo Jing Hua Zhao Ayşe Demirkan Mary F. Feitosa Xuan Li Giovanni Malerba Lorna M. Lopez Pim van der Harst Xinzhong Li Marcus E. Kleber Andrew A. Hicks Ilja M. Nolte Åsa 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 Gíslason Tamara B. Harris Lenore J. Launer Patrick F. 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 Péter Vollenweider Gérard Waeber Susan Campbell Olivier Devuyst Pau Navarro Ivana Kolčić Nicholas D. Hastie Beverley Balkau Philippe Froguel Tõnu Esko Andres Salumets Kay Tee Khaw Claudia Langenberg Nicholas J. Wareham Aaron Isaacs Aldi T. Kraja Qunyuan Zhang Philipp S. Wild Rodney J. Scott Elizabeth G. Holliday Elin Org Margus Viigimaa Stefania Bandinelli Jeffrey Metter Antonio Lupo Elisabetta Trabetti Rossella Sorice Angela Döring Eva Lattka Konstantin Strauch Fabian J. Theis Mélanie Waldenberger Heinz‐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. J. H. Penninx Johannes H. Smit Gary C. 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 André 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 Τheodoratou Inga Prokopenko Michael Stümvoll 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 Singleton Naoyuki Kamatani Tanja Zeller Michel Burnier John Attia Maris Laan Norman Klopp Hans L. Hillege Stefan Kloiber Hyon K. Choi Mario Pirastu Silvia Tore Nicole 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 T. Raitakari W. H. Linda Kao Marina Ciullo Caroline S. Fox Mark J. Caulfield Murielle Bochud Christian Gieger published in 2012. It has an Open Access status of “green”. You can read and download a PDF Full Text of this paper here.