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

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, Zoltán Kutalik, Albert V. Smith, Julia Shi, Maksim Struchalin, Rita P S Middelberg, Morris J. Brown, Angelo L. Gaffo & 205 others 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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)145-154
Number of pages10
JournalNature Genetics
Volume45
Issue number2
DOIs
StatePublished - Feb 1 2013

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Genome-Wide Association Study
Uric Acid
Serum
Gout
Activins
Inhibins
Arthritis
Genome
Glucose
Genes

ASJC Scopus subject areas

  • Genetics

Cite this

Köttgen, A., Albrecht, E., Teumer, A., Vitart, V., Krumsiek, J., Hundertmark, C., ... Gieger, C. (2013). Genome-wide association analyses identify 18 new loci associated with serum urate concentrations. Nature Genetics, 45(2), 145-154. https://doi.org/10.1038/ng.2500

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

In: Nature Genetics, Vol. 45, No. 2, 01.02.2013, p. 145-154.

Research output: Contribution to journalArticle

Köttgen, A, Albrecht, E, Teumer, A, Vitart, V, Krumsiek, J, Hundertmark, C, Pistis, G, Ruggiero, D, O'Seaghdha, CM, Haller, T, Yang, Q, Tanaka, T, Johnson, AD, Kutalik, Z, Smith, AV, Shi, J, Struchalin, M, Middelberg, RPS, Brown, MJ, Gaffo, AL, Pirastu, N, Li, G, Hayward, C, Zemunik, T, Huffman, J, Yengo, L, Zhao, JH, Demirkan, A, Feitosa, MF, Liu, X, Malerba, G, Lopez, LM, Van Der Harst, P, Li, X, Kleber, ME, Hicks, AA, Nolte, IM, Johansson, A, Murgia, F, Wild, SH, Bakker, SJL, Peden, JF, Dehghan, A, Steri, M, Tenesa, A, Lagou, V, Salo, P, Mangino, M, Rose, LM, Lehtimäki, T, Woodward, OM, Okada, Y, Tin, A, Müller, C, Oldmeadow, C, Putku, M, Czamara, D, Kraft, P, Frogheri, L, Thun, GA, Grotevendt, A, Gislason, GK, Harris, TB, Launer, LJ, McArdle, P, Shuldiner, AR, Boerwinkle, E, Coresh, J, Schmidt, H, Schallert, M, Martin, NG, Montgomery, GW, Kubo, M, Nakamura, Y, Tanaka, T, Munroe, PB, Samani, NJ, Jacobs, DR, Liu, K, D'Adamo, P, Ulivi, S, Rotter, JI, Psaty, BM, Vollenweider, P, Waeber, G, Campbell, S, Devuyst, O, Navarro, P, Kolcic, I, Hastie, N, Balkau, B, Froguel, P, Esko, T, Salumets, A, Khaw, KT, Langenberg, C, Wareham, NJ, Isaacs, A, Kraja, A, Zhang, Q, Wild, PS, Scott, RJ, Holliday, EG, Org, E, Viigimaa, M, Bandinelli, S, Metter, JE, Lupo, A, Trabetti, E, Sorice, R, Döring, A, Lattka, E, Strauch, K, Theis, F, Waldenberger, M, Wichmann, HE, Davies, G, Gow, AJ, Bruinenberg, M, Stolk, RP, Kooner, JS, Zhang, W, Winkelmann, BR, Boehm, BO, Lucae, S, Penninx, BW, Smit, JH, Curhan, G, Mudgal, P, Plenge, RM, Portas, L, Persico, I, Kirin, M, Wilson, JF, Leach, IM, Van Gilst, WH, Goel, A, Ongen, H, Hofman, A, Rivadeneira, F, Uitterlinden, AG, Imboden, M, Von Eckardstein, A, Cucca, F, Nagaraja, R, Piras, MG, Nauck, M, Schurmann, C, Budde, K, Ernst, F, Farrington, SM, Theodoratou, E, Prokopenko, I, Stumvoll, M, Jula, A, Perola, M, Salomaa, V, Shin, SY, Spector, TD, Sala, C, Ridker, PM, Kähönen, M, Viikari, J, Hengstenberg, C, Nelson, CP, Meschia, JF, Nalls, MA, Sharma, P, Singleton, AB, Kamatani, N, Zeller, T, Burnier, M, Attia, J, Laan, M, Klopp, N, Hillege, HL, Kloiber, S, Choi, H, Pirastu, M, Tore, S, Probst-Hensch, NM, Völzke, H, Gudnason, V, Parsa, A, Schmidt, R, Whitfield, JB, Fornage, M, Gasparini, P, Siscovick, DS, Polašek, O, Campbell, H, Rudan, I, Bouatia-Naji, N, Metspalu, A, Loos, RJF, Van Duijn, CM, Borecki, IB, Ferrucci, L, Gambaro, G, Deary, IJ, Wolffenbuttel, BHR, Chambers, JC, März, W, Pramstaller, PP, Snieder, H, Gyllensten, U, Wright, AF, Navis, G, Watkins, H, Witteman, JCM, Sanna, S, Schipf, S, Dunlop, MG, Tönjes, A, Ripatti, S, Soranzo, N, Toniolo, D, Chasman, DI, Raitakari, O, Kao, WHL, Ciullo, M, Fox, CS, Caulfield, M, Bochud, M & Gieger, C 2013, 'Genome-wide association analyses identify 18 new loci associated with serum urate concentrations', Nature Genetics, vol. 45, no. 2, pp. 145-154. https://doi.org/10.1038/ng.2500
Köttgen A, Albrecht E, Teumer A, Vitart V, Krumsiek J, Hundertmark C et al. Genome-wide association analyses identify 18 new loci associated with serum urate concentrations. Nature Genetics. 2013 Feb 1;45(2):145-154. https://doi.org/10.1038/ng.2500
Köttgen, Anna ; Albrecht, Eva ; Teumer, Alexander ; Vitart, Veronique ; Krumsiek, Jan ; Hundertmark, Claudia ; Pistis, Giorgio ; Ruggiero, Daniela ; O'Seaghdha, Conall M. ; Haller, Toomas ; Yang, Qiong ; Tanaka, Toshiko ; Johnson, Andrew D. ; Kutalik, Zoltán ; Smith, Albert V. ; Shi, Julia ; Struchalin, Maksim ; Middelberg, Rita P S ; Brown, Morris J. ; Gaffo, Angelo L. ; Pirastu, Nicola ; Li, Guo ; Hayward, Caroline ; Zemunik, Tatijana ; Huffman, Jennifer ; Yengo, Loic ; Zhao, Jing Hua ; Demirkan, Ayse ; Feitosa, Mary F. ; Liu, Xuan ; Malerba, Giovanni ; Lopez, Lorna M. ; Van Der Harst, Pim ; Li, Xinzhong ; Kleber, Marcus E. ; Hicks, Andrew A. ; Nolte, Ilja M. ; Johansson, Asa ; Murgia, Federico ; Wild, Sarah H. ; Bakker, Stephan J L ; Peden, John F. ; Dehghan, Abbas ; Steri, Maristella ; Tenesa, Albert ; Lagou, Vasiliki ; Salo, Perttu ; Mangino, Massimo ; Rose, Lynda M. ; Lehtimäki, Terho ; Woodward, Owen M. ; Okada, Yukinori ; Tin, Adrienne ; Müller, Christian ; Oldmeadow, Christopher ; Putku, Margus ; Czamara, Darina ; Kraft, Peter ; Frogheri, Laura ; Thun, Gian Andri ; Grotevendt, Anne ; Gislason, Gauti Kjartan ; Harris, Tamara B. ; Launer, Lenore J. ; McArdle, Patrick ; Shuldiner, Alan R. ; Boerwinkle, Eric ; Coresh, Josef ; Schmidt, Helena ; Schallert, Michael ; Martin, Nicholas G. ; Montgomery, Grant W. ; Kubo, Michiaki ; Nakamura, Yusuke ; Tanaka, Toshihiro ; Munroe, Patricia B. ; Samani, Nilesh J. ; Jacobs, David R. ; Liu, Kiang ; D'Adamo, Pio ; Ulivi, Sheila ; Rotter, Jerome I. ; Psaty, Bruce M. ; Vollenweider, Peter ; Waeber, Gerard ; Campbell, Susan ; Devuyst, Olivier ; Navarro, Pau ; Kolcic, Ivana ; Hastie, Nicholas ; Balkau, Beverley ; Froguel, Philippe ; Esko, Tõnu ; Salumets, Andres ; Khaw, Kay Tee ; Langenberg, Claudia ; Wareham, Nicholas J. ; Isaacs, Aaron ; Kraja, Aldi ; Zhang, Qunyuan ; Wild, Philipp S. ; Scott, Rodney J. ; Holliday, Elizabeth G. ; Org, Elin ; Viigimaa, Margus ; Bandinelli, Stefania ; Metter, Jeffrey E. ; Lupo, Antonio ; Trabetti, Elisabetta ; Sorice, Rossella ; Döring, Angela ; Lattka, Eva ; Strauch, Konstantin ; Theis, Fabian ; Waldenberger, Melanie ; Wichmann, H. Erich ; Davies, Gail ; Gow, Alan J. ; Bruinenberg, Marcel ; Stolk, Ronald P. ; Kooner, Jaspal S. ; Zhang, Weihua ; Winkelmann, Bernhard R. ; Boehm, Bernhard O. ; Lucae, Susanne ; Penninx, Brenda W. ; Smit, Johannes H. ; Curhan, Gary ; Mudgal, Poorva ; Plenge, Robert M. ; Portas, Laura ; Persico, Ivana ; Kirin, Mirna ; Wilson, James F. ; Leach, Irene Mateo ; Van Gilst, Wiek H. ; Goel, Anuj ; Ongen, Halit ; Hofman, Albert ; Rivadeneira, Fernando ; Uitterlinden, Andre G. ; Imboden, Medea ; Von Eckardstein, Arnold ; Cucca, Francesco ; Nagaraja, Ramaiah ; Piras, Maria Grazia ; Nauck, Matthias ; Schurmann, Claudia ; Budde, Kathrin ; Ernst, Florian ; Farrington, Susan M. ; Theodoratou, Evropi ; Prokopenko, Inga ; Stumvoll, Michael ; Jula, Antti ; Perola, Markus ; Salomaa, Veikko ; Shin, So Youn ; Spector, Tim D. ; Sala, Cinzia ; Ridker, Paul M. ; Kähönen, Mika ; Viikari, Jorma ; Hengstenberg, Christian ; Nelson, Christopher P. ; Meschia, James F. ; Nalls, Michael A. ; Sharma, Pankaj ; Singleton, Andrew B. ; Kamatani, Naoyuki ; Zeller, Tanja ; Burnier, Michel ; Attia, John ; Laan, Maris ; Klopp, Norman ; Hillege, Hans L. ; Kloiber, Stefan ; Choi, Hyon ; Pirastu, Mario ; Tore, Silvia ; Probst-Hensch, Nicole M. ; Völzke, Henry ; Gudnason, Vilmundur ; Parsa, Afshin ; Schmidt, Reinhold ; Whitfield, John B. ; Fornage, Myriam ; Gasparini, Paolo ; Siscovick, David S. ; Polašek, Ozren ; Campbell, Harry ; Rudan, Igor ; Bouatia-Naji, Nabila ; Metspalu, Andres ; Loos, Ruth J F ; Van Duijn, Cornelia M. ; Borecki, Ingrid B. ; Ferrucci, Luigi ; Gambaro, Giovanni ; Deary, Ian J. ; Wolffenbuttel, Bruce H R ; Chambers, John C. ; März, Winfried ; Pramstaller, Peter P. ; Snieder, Harold ; Gyllensten, Ulf ; Wright, Alan F. ; Navis, Gerjan ; Watkins, Hugh ; Witteman, Jacqueline C M ; Sanna, Serena ; Schipf, Sabine ; Dunlop, Malcolm G. ; Tönjes, Anke ; Ripatti, Samuli ; Soranzo, Nicole ; Toniolo, Daniela ; Chasman, Daniel I. ; Raitakari, Olli ; Kao, W. H Linda ; Ciullo, Marina ; Fox, Caroline S. ; Caulfield, Mark ; Bochud, Murielle ; Gieger, Christian. / Genome-wide association analyses identify 18 new loci associated with serum urate concentrations. In: Nature Genetics. 2013 ; Vol. 45, No. 2. pp. 145-154.
@article{a1129c37faa54beb8e023c26f998b5a4,
title = "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.",
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 O'Seaghdha, {Conall M.} and Toomas Haller and Qiong Yang and Toshiko Tanaka and Johnson, {Andrew D.} and Zolt{\'a}n Kutalik and Smith, {Albert V.} and Julia Shi and Maksim Struchalin and Middelberg, {Rita P S} and Brown, {Morris J.} and Gaffo, {Angelo L.} and Nicola Pirastu and Guo Li and Caroline Hayward and Tatijana Zemunik and Jennifer Huffman and Loic Yengo and Zhao, {Jing Hua} and Ayse Demirkan and Feitosa, {Mary F.} and Xuan Liu and Giovanni Malerba and Lopez, {Lorna M.} and {Van Der Harst}, Pim and Xinzhong Li and Kleber, {Marcus E.} and Hicks, {Andrew A.} and Nolte, {Ilja M.} and Asa Johansson and Federico Murgia and Wild, {Sarah H.} and Bakker, {Stephan J L} and Peden, {John F.} and Abbas Dehghan and Maristella Steri and Albert Tenesa and Vasiliki Lagou and Perttu Salo and Massimo Mangino and Rose, {Lynda M.} and Terho Lehtim{\"a}ki and Woodward, {Owen M.} 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 Thun, {Gian Andri} and Anne Grotevendt and Gislason, {Gauti Kjartan} and Harris, {Tamara B.} and Launer, {Lenore J.} and Patrick McArdle and Shuldiner, {Alan R.} and Eric Boerwinkle and Josef Coresh and Helena Schmidt and Michael Schallert and Martin, {Nicholas G.} and Montgomery, {Grant W.} and Michiaki Kubo and Yusuke Nakamura and Toshihiro Tanaka and Munroe, {Patricia B.} and Samani, {Nilesh J.} and Jacobs, {David R.} and Kiang Liu and Pio D'Adamo and Sheila Ulivi and Rotter, {Jerome I.} and Psaty, {Bruce M.} and Peter Vollenweider and Gerard Waeber and Susan Campbell and Olivier Devuyst and Pau Navarro and Ivana Kolcic and Nicholas Hastie and Beverley Balkau and Philippe Froguel and T{\~o}nu Esko and Andres Salumets and Khaw, {Kay Tee} and Claudia Langenberg and Wareham, {Nicholas J.} and Aaron Isaacs and Aldi Kraja and Qunyuan Zhang and Wild, {Philipp S.} and Scott, {Rodney J.} and Holliday, {Elizabeth G.} and Elin Org and Margus Viigimaa and Stefania Bandinelli and Metter, {Jeffrey E.} and Antonio Lupo and Elisabetta Trabetti and Rossella Sorice and Angela D{\"o}ring and Eva Lattka and Konstantin Strauch and Fabian Theis and Melanie Waldenberger and Wichmann, {H. Erich} and Gail Davies and Gow, {Alan J.} and Marcel Bruinenberg and Stolk, {Ronald P.} and Kooner, {Jaspal S.} and Weihua Zhang and Winkelmann, {Bernhard R.} and Boehm, {Bernhard O.} and Susanne Lucae and Penninx, {Brenda W.} and Smit, {Johannes H.} and Gary Curhan and Poorva Mudgal and Plenge, {Robert M.} and Laura Portas and Ivana Persico and Mirna Kirin and Wilson, {James F.} and Leach, {Irene Mateo} and {Van Gilst}, {Wiek H.} and Anuj Goel and Halit Ongen and Albert Hofman and Fernando Rivadeneira and Uitterlinden, {Andre G.} and Medea Imboden and {Von Eckardstein}, Arnold and Francesco Cucca and Ramaiah Nagaraja and Piras, {Maria Grazia} and Matthias Nauck and Claudia Schurmann and Kathrin Budde and Florian Ernst and Farrington, {Susan M.} and Evropi Theodoratou and Inga Prokopenko and Michael Stumvoll and Antti Jula and Markus Perola and Veikko Salomaa and Shin, {So Youn} and Spector, {Tim D.} and Cinzia Sala and Ridker, {Paul M.} and Mika K{\"a}h{\"o}nen and Jorma Viikari and Christian Hengstenberg and Nelson, {Christopher P.} and Meschia, {James F.} and Nalls, {Michael A.} and Pankaj Sharma and Singleton, {Andrew B.} and Naoyuki Kamatani and Tanja Zeller and Michel Burnier and John Attia and Maris Laan and Norman Klopp and Hillege, {Hans L.} and Stefan Kloiber and Hyon Choi and Mario Pirastu and Silvia Tore and Probst-Hensch, {Nicole M.} and Henry V{\"o}lzke and Vilmundur Gudnason and Afshin Parsa and Reinhold Schmidt and Whitfield, {John B.} and Myriam Fornage and Paolo Gasparini and Siscovick, {David S.} and Ozren Polašek and Harry Campbell and Igor Rudan and Nabila Bouatia-Naji and Andres Metspalu and Loos, {Ruth J F} and {Van Duijn}, {Cornelia M.} and Borecki, {Ingrid B.} and Luigi Ferrucci and Giovanni Gambaro and Deary, {Ian J.} and Wolffenbuttel, {Bruce H R} and Chambers, {John C.} and Winfried M{\"a}rz and Pramstaller, {Peter P.} and Harold Snieder and Ulf Gyllensten and Wright, {Alan F.} and Gerjan Navis and Hugh Watkins and Witteman, {Jacqueline C M} and Serena Sanna and Sabine Schipf and Dunlop, {Malcolm G.} and Anke T{\"o}njes and Samuli Ripatti and Nicole Soranzo and Daniela Toniolo and Chasman, {Daniel I.} and Olli Raitakari and Kao, {W. H Linda} and Marina Ciullo and Fox, {Caroline S.} and Mark Caulfield and Murielle Bochud and Christian Gieger",
year = "2013",
month = "2",
day = "1",
doi = "10.1038/ng.2500",
language = "English (US)",
volume = "45",
pages = "145--154",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "2",

}

TY - JOUR

T1 - Genome-wide association analyses identify 18 new loci associated with serum urate concentrations

AU - Köttgen, Anna

AU - Albrecht, Eva

AU - Teumer, Alexander

AU - Vitart, Veronique

AU - Krumsiek, Jan

AU - Hundertmark, Claudia

AU - Pistis, Giorgio

AU - Ruggiero, Daniela

AU - O'Seaghdha, Conall M.

AU - Haller, Toomas

AU - Yang, Qiong

AU - Tanaka, Toshiko

AU - Johnson, Andrew D.

AU - Kutalik, Zoltán

AU - Smith, Albert V.

AU - Shi, Julia

AU - Struchalin, Maksim

AU - Middelberg, Rita P S

AU - Brown, Morris J.

AU - Gaffo, Angelo L.

AU - Pirastu, Nicola

AU - Li, Guo

AU - Hayward, Caroline

AU - Zemunik, Tatijana

AU - Huffman, Jennifer

AU - Yengo, Loic

AU - Zhao, Jing Hua

AU - Demirkan, Ayse

AU - Feitosa, Mary F.

AU - Liu, Xuan

AU - Malerba, Giovanni

AU - Lopez, Lorna M.

AU - Van Der Harst, Pim

AU - Li, Xinzhong

AU - Kleber, Marcus E.

AU - Hicks, Andrew A.

AU - Nolte, Ilja M.

AU - Johansson, Asa

AU - Murgia, Federico

AU - Wild, Sarah H.

AU - Bakker, Stephan J L

AU - Peden, John F.

AU - Dehghan, Abbas

AU - Steri, Maristella

AU - Tenesa, Albert

AU - Lagou, Vasiliki

AU - Salo, Perttu

AU - Mangino, Massimo

AU - Rose, Lynda M.

AU - Lehtimäki, Terho

AU - Woodward, Owen M.

AU - Okada, Yukinori

AU - Tin, Adrienne

AU - Müller, Christian

AU - Oldmeadow, Christopher

AU - Putku, Margus

AU - Czamara, Darina

AU - Kraft, Peter

AU - Frogheri, Laura

AU - Thun, Gian Andri

AU - Grotevendt, Anne

AU - Gislason, Gauti Kjartan

AU - Harris, Tamara B.

AU - Launer, Lenore J.

AU - McArdle, Patrick

AU - Shuldiner, Alan R.

AU - Boerwinkle, Eric

AU - Coresh, Josef

AU - Schmidt, Helena

AU - Schallert, Michael

AU - Martin, Nicholas G.

AU - Montgomery, Grant W.

AU - Kubo, Michiaki

AU - Nakamura, Yusuke

AU - Tanaka, Toshihiro

AU - Munroe, Patricia B.

AU - Samani, Nilesh J.

AU - Jacobs, David R.

AU - Liu, Kiang

AU - D'Adamo, Pio

AU - Ulivi, Sheila

AU - Rotter, Jerome I.

AU - Psaty, Bruce M.

AU - Vollenweider, Peter

AU - Waeber, Gerard

AU - Campbell, Susan

AU - Devuyst, Olivier

AU - Navarro, Pau

AU - Kolcic, Ivana

AU - Hastie, Nicholas

AU - Balkau, Beverley

AU - Froguel, Philippe

AU - Esko, Tõnu

AU - Salumets, Andres

AU - Khaw, Kay Tee

AU - Langenberg, Claudia

AU - Wareham, Nicholas J.

AU - Isaacs, Aaron

AU - Kraja, Aldi

AU - Zhang, Qunyuan

AU - Wild, Philipp S.

AU - Scott, Rodney J.

AU - Holliday, Elizabeth G.

AU - Org, Elin

AU - Viigimaa, Margus

AU - Bandinelli, Stefania

AU - Metter, Jeffrey E.

AU - Lupo, Antonio

AU - Trabetti, Elisabetta

AU - Sorice, Rossella

AU - Döring, Angela

AU - Lattka, Eva

AU - Strauch, Konstantin

AU - Theis, Fabian

AU - Waldenberger, Melanie

AU - Wichmann, H. Erich

AU - Davies, Gail

AU - Gow, Alan J.

AU - Bruinenberg, Marcel

AU - Stolk, Ronald P.

AU - Kooner, Jaspal S.

AU - Zhang, Weihua

AU - Winkelmann, Bernhard R.

AU - Boehm, Bernhard O.

AU - Lucae, Susanne

AU - Penninx, Brenda W.

AU - Smit, Johannes H.

AU - Curhan, Gary

AU - Mudgal, Poorva

AU - Plenge, Robert M.

AU - Portas, Laura

AU - Persico, Ivana

AU - Kirin, Mirna

AU - Wilson, James F.

AU - Leach, Irene Mateo

AU - Van Gilst, Wiek H.

AU - Goel, Anuj

AU - Ongen, Halit

AU - Hofman, Albert

AU - Rivadeneira, Fernando

AU - Uitterlinden, Andre G.

AU - Imboden, Medea

AU - Von Eckardstein, Arnold

AU - Cucca, Francesco

AU - Nagaraja, Ramaiah

AU - Piras, Maria Grazia

AU - Nauck, Matthias

AU - Schurmann, Claudia

AU - Budde, Kathrin

AU - Ernst, Florian

AU - Farrington, Susan M.

AU - Theodoratou, Evropi

AU - Prokopenko, Inga

AU - Stumvoll, Michael

AU - Jula, Antti

AU - Perola, Markus

AU - Salomaa, Veikko

AU - Shin, So Youn

AU - Spector, Tim D.

AU - Sala, Cinzia

AU - Ridker, Paul M.

AU - Kähönen, Mika

AU - Viikari, Jorma

AU - Hengstenberg, Christian

AU - Nelson, Christopher P.

AU - Meschia, James F.

AU - Nalls, Michael A.

AU - Sharma, Pankaj

AU - Singleton, Andrew B.

AU - Kamatani, Naoyuki

AU - Zeller, Tanja

AU - Burnier, Michel

AU - Attia, John

AU - Laan, Maris

AU - Klopp, Norman

AU - Hillege, Hans L.

AU - Kloiber, Stefan

AU - Choi, Hyon

AU - Pirastu, Mario

AU - Tore, Silvia

AU - Probst-Hensch, Nicole M.

AU - Völzke, Henry

AU - Gudnason, Vilmundur

AU - Parsa, Afshin

AU - Schmidt, Reinhold

AU - Whitfield, John B.

AU - Fornage, Myriam

AU - Gasparini, Paolo

AU - Siscovick, David S.

AU - Polašek, Ozren

AU - Campbell, Harry

AU - Rudan, Igor

AU - Bouatia-Naji, Nabila

AU - Metspalu, Andres

AU - Loos, Ruth J F

AU - Van Duijn, Cornelia M.

AU - Borecki, Ingrid B.

AU - Ferrucci, Luigi

AU - Gambaro, Giovanni

AU - Deary, Ian J.

AU - Wolffenbuttel, Bruce H R

AU - Chambers, John C.

AU - März, Winfried

AU - Pramstaller, Peter P.

AU - Snieder, Harold

AU - Gyllensten, Ulf

AU - Wright, Alan F.

AU - Navis, Gerjan

AU - Watkins, Hugh

AU - Witteman, Jacqueline C M

AU - Sanna, Serena

AU - Schipf, Sabine

AU - Dunlop, Malcolm G.

AU - Tönjes, Anke

AU - Ripatti, Samuli

AU - Soranzo, Nicole

AU - Toniolo, Daniela

AU - Chasman, Daniel I.

AU - Raitakari, Olli

AU - Kao, W. H Linda

AU - Ciullo, Marina

AU - Fox, Caroline S.

AU - Caulfield, Mark

AU - Bochud, Murielle

AU - Gieger, Christian

PY - 2013/2/1

Y1 - 2013/2/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84947899575&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84947899575&partnerID=8YFLogxK

U2 - 10.1038/ng.2500

DO - 10.1038/ng.2500

M3 - Article

VL - 45

SP - 145

EP - 154

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 2

ER -