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

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

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Albert V. Smith
d'Adamo et al., 2012

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@article{d'Adamo2012,
  abstract = {Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from &gt;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 = {d'Adamo, Pio and Teumer, Alexander and Vitart, Veronique and Tee Khaw, Kay and Rp, Middelberg and Pistis, Giorgio and Ruggiero, Daniela and O'Seaghdha, Cm M. and Yang, Qiong and Sh, Wild and Smith, Albert V. and Sj, Bakker and Shi, Julia and Om, Woodward and Struchalin, Maksim and Tönjes, Anke and Pirastu, Nicola and van der Harst, Pim and O’seaghdha, Conall M. and Tb, Harris and Köttgen, Anna and Zemunik, Tatijana and Van Der Harst, P. and Albrecht, Eva and Yengo, Loïc and Ng, Martin and Pb, Munroe and Zhao, Jing Hua and Krumsiek, Jan and Tanaka, Toshiko and Hundertmark, Claudia and Nj, Samani and Nj, Wareham and Haller, Toomas and Ps, Wild and Nolte, Ilja M. and Johnson, Andrew D. and Rj, Scott and Kutalik, Zoltán and Wild, Sarah H. and Peden, John F. and Rp, Stolk and Middelberg, Rita P. S. and Steri, Maristella and Tenesa, Albert and Brown, Morris J. and Gaffo, Angelo L. and Salo, Perttu and Li, Guo and Rose, Lynda M. and Rm, Plenge and Hayward, Caroline and Woodward, Owen M. and Huffman, Jennifer and Okada, Yukinori and Tin, Adrienne and Wh, van Gilst and Müller, Christian and Demirkan, Ayşe and Oldmeadow, Christopher and Putku, Margus and Feitosa, Mary F. and Liu, Xuan and Tanaka, Toshihiro and Malerba, Giovanni and Thun, Gian Andri and Sm, Farrington and Lopez, Lorna M. and Sy, Shin and Li, Xinzhong and Shuldiner, Alan R. and Kleber, Marcus E. and Td, Spector and Schmidt, Helena and Hicks, Andrew Aa and Schallert, Michael and Pm, Ridker and Johansson, Åsa and Nakamura, Yusuke and Bakker, Stephan J. L. and Dehghan, Abbas and Samani, Nilesh J. and Lagou, Vasiliki and Ulivi, Sheila and Mangino, Massimo and Rotter, Jerome I. and Nm, Probst Hensch and Psaty, Bruce M. and Lehtimäki, Terho and Vollenweider, Peter and Waeber, Gerard and Voelzke, Henry and Rj, Loos and van Gilst, Wiek H. and Navarro, Pau and Czamara, Darina and Murgia, Federico and Kraft, Peter and Frogheri, Laura and von Eckardstein, Arnold and Salumets, Andres and Grotevendt, Anne and Gislason, Gauti Kjartan and Wareham, Nicholas J. and Harris, Tamara B. and Study, LifeLines Cohort and Launer, Lenore J. and Wild, Philipp S. and Pp, Pramstaller and Zhang, Qunyuan and McArdle, Patrick and Scott, Rodney J. and Boerwinkle, Eric and Org, Elin and Coresh, Josef and Viigimaa, Margus and Toenjes, Anke and Martin, Nicholas G. and Trabetti, Elisabetta and Van Gilst, W. H. and Montgomery, Grant W. and Sorice, Rossella and Kubo, Michiaki and Wh, Kao and Strauch, Konstantin and Munroe, Patricia B. and Theis, Fabian and Others,  and Waldenberger, Melanie and Jacobs, David R. J. R. and Wichmann, He-Erich and Liu, Kiang and Von Eckardstein, A. and Koettgen, Anna and Stolk, Ronald P. and Zhang, Weihua and Av, Smith and van Duijn, Cornelia M. and Winkelmann, Bernhard R. and Mj, Brown and Campbell, Susan and Penninx, Brenda W. and Devuyst, Olivier and Al, Gaffo and Smit, Johannes H. and Kolcic, Ivana and Jh, Zhao and Plenge, Robert M. and Hastie, Nicholas and Portas, Laura and Mf, Feitosa and Persico, Ivana and Balkau, Beverley and Froguel, Philippe and Wilson, James F. and Esko, Tõnu and Lm, Lopez and Khaw, Kay Tee and Me, Kleber and Langenberg, Claudia and Ongen, Halit and Isaacs, Aaron and Aa, Hicks and Rivadeneira, Fernando and Kraja, Aldi and Im, Nolte and Uitterlinden, Andre G. and Holliday, Elizabeth G. and Nagaraja, Ramaiah and Jf, Peden and Piras, Maria Grazia and Bandinelli, Stefania and Nauck, Matthias and Kottgen, A. and Metter, Jeffrey E. and Schurmann, Claudia and Lupo, Antonio and Lm, Rose and Döring, Angela and Lattka, Eva and Theodoratou, Evropi and Mueller, Christian and Prokopenko, Inga and Ga, Thun and Stumvoll, Michael and Gk, Gislason and Perola, Markus and Davies, Gail and Gow, Alan J. and Salomaa, Veikko and Bruinenberg, Marcel and Lj, Launer and Shin, So-Youn and Spector, Tim D. and Kooner, Jaspal S. and Ar, Shuldiner and Sala, Cinzia and Ridker, Paul M. and Boehm, Bernhard O. and Gw, Montgomery and Viikari, Jorma and Lucae, Susanne and Nelson, Christopher P. and Cm, O'Seaghdha and Nalls, Michael A. and Curhan, Gary and Sharma, Pankaj and Mudgal, Poorva and Singleton, Andrew B. and Dr, Jacobs and Ji, Rotter and Van Duijn, C. M. and Zeller, Tanja and Bm, Psaty and Kirin, Mirna and Leach, Irene Mateo and Kt, Khaw and D’Adamo, Pio and Goel, Anuj and Pirastu, Mario and Hofman, Albert and Tore, Silvia and Probst-Hensch, Nicole M. and Imboden, Medea and Eg, Holliday and Völzke, Henry and Je, Metter and Cucca, Francesco and Parsa, Afshin and He, Wichmann and Schmidt, Reinhold and Budde, Kathrin and Whitfield, John B. and Ernst, Florian and Aj, Gow and Farrington, Susan M. and Ad, Johnson and Siscovick, David S. and Polasek, Ozren and Doering, Angela and Jula, Antti and Rudan, Igor and Erich Wichmann, H. and Kähönen, Mika and Hengstenberg, Christian and Js, Kooner and Meschia, James F. and Wolffenbuttel, Bruce H. R. and Br, Winkelmann and März, Winfried and Bo, Boehm and Kamatani, Naoyuki and Pramstaller, Peter Pp and Burnier, Michel and Bw, Penninx and Snieder, Harold and Jh, Smit and Attia, John and Laan, Maris and Jf, Wilson and Wright, Alan F. and Im, Leach and Klopp, Norman and Navis, Gerjan and Hillege, Hans L. and Ag, Uitterlinden and Kloiber, Stefan and Watkins, Hugh and Mateo Leach, Irene and Choi, Hyon and Witteman, Jacqueline C. M. and Mg, Piras and Sanna, Serena and Schipf, Sabine and Gudnason, Vilmundur and Cp, Nelson and Tönjes, Anke and Kaehoenen, Mika and Ripatti, Samuli and Fornage, Myriam and Soranzo, Nicole and Jf, Meschia and Gasparini, Paolo and Toniolo, Daniela and Ma, Nalls and Campbell, Harry and Ab, Singleton and Raitakari, Olli and Hl, Hillege and Bouatia-Naji, Nabila and Jb, Whitfield and Metspalu, Andres and Loos, Ruth J. F. and Ds, Siscovick and Cm, van Duijn and Borecki, Ingrid B. and Diagram, Consortium and Ferrucci, Luigi and Gambaro, Giovanni and Ib, Borecki and Deary, Ian J. and Icbp, Consortium and Ij, Deary and Chambers, John C. and Bh, Wolffenbuttel and Gyllensten, Ulf and Magic, Consortium and Maerz, Winfried and Jc, Chambers and Consortium, CARDIoGRAM and Dunlop, Malcolm G. and Kahonen, Mika and Af, Wright and Jc, Witteman and Mg, Dunlop and März, Winfried and Chasman, Daniel I. and Di, Chasman and Kao, Wh H. Linda and Ciullo, Marina and Fox, Caroline S. and Cs, Fox and Caulfield, Mark and Bochud, Murielle and Linda Kao, W. H. and Gieger, Christian},
  doi = {10.1038/ng.2500},
  month = {dec},
  title = {Genome-wide association analyses identify 18 new loci associated with serum urate concentrations},
  url = {http://www.nature.com/articles/ng.2500.pdf},
  year = {2012}
}

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

Journal article published in 2012 by Pio d'Adamo, Alexander Teumer, Veronique Vitart, Kay Tee Khaw, Middelberg Rp, Giorgio Pistis, Daniela Ruggiero, Cm M. O'Seaghdha, Qiong Yang, Wild Sh, Albert V. Smith

, Bakker Sj, Julia Shi, Woodward Om, Maksim Struchalin and other authors. Pio d'Adamo, Alexander Teumer, Veronique Vitart, Kay Tee Khaw, Middelberg Rp, Giorgio Pistis, Daniela Ruggiero, Cm M. O'Seaghdha, Qiong Yang, Wild Sh, Albert V. Smith

, Bakker Sj, Julia Shi, Woodward Om, Maksim Struchalin, Anke Tönjes, Nicola Pirastu, Pim van der Harst, Conall M. O’seaghdha, Harris Tb, Anna Köttgen, Tatijana Zemunik, P. Van Der Harst, Eva Albrecht, Loïc Yengo, Martin Ng, Munroe Pb, Jing Hua Zhao, Jan Krumsiek, Toshiko Tanaka

, Claudia Hundertmark, Samani Nj, Wareham Nj, Toomas Haller, Wild Ps, Ilja M. Nolte, Andrew D. Johnson, Scott Rj, Zoltán Kutalik, Sarah H. Wild, John F. Peden, Stolk Rp, Rita P. S. Middelberg, Maristella Steri

, Albert Tenesa, Morris J. Brown, Angelo L. Gaffo

, Perttu Salo, Guo Li, Lynda M. Rose, Plenge Rm, Caroline Hayward, Owen M. Woodward, Jennifer Huffman, Yukinori Okada, Adrienne Tin, van Gilst Wh, Christian Müller, Ayşe Demirkan, Christopher Oldmeadow, Margus Putku, Mary F. Feitosa, Xuan Liu, Toshihiro Tanaka, Giovanni Malerba, Gian Andri Thun, Farrington Sm, Lorna M. Lopez, Shin Sy, Xinzhong Li, Alan R. Shuldiner, Marcus E. Kleber, Spector Td, Helena Schmidt, Andrew Aa Hicks, Michael Schallert, Ridker Pm, Åsa Johansson, Yusuke Nakamura, Stephan J. L. Bakker, Abbas Dehghan

, Nilesh J. Samani, Vasiliki Lagou, Sheila Ulivi, Massimo Mangino, Jerome I. Rotter, Probst Hensch Nm, Bruce M. Psaty, Terho Lehtimäki, Peter Vollenweider, Gerard Waeber, Henry Voelzke, Loos Rj, Wiek H. van Gilst, Pau Navarro

, Darina Czamara, Federico Murgia

, Peter Kraft, Laura Frogheri, Arnold von Eckardstein, Andres Salumets, Anne Grotevendt, Gauti Kjartan Gislason, Nicholas J. Wareham, Tamara B. Harris, LifeLines Cohort Study, Lenore J. Launer, Philipp S. Wild, Pramstaller Pp, Qunyuan Zhang, Patrick McArdle, Rodney J. Scott, Eric Boerwinkle, Elin Org, Josef Coresh, Margus Viigimaa, Anke Toenjes, Nicholas G. Martin, Elisabetta Trabetti, W. H. Van Gilst, Grant W. Montgomery, Rossella Sorice, Michiaki Kubo, Kao Wh, Konstantin Strauch, Patricia B. Munroe, Fabian Theis, Others, Melanie Waldenberger, David R. J. R. Jacobs, He-Erich Wichmann, Kiang Liu, A. Von Eckardstein, Anna Koettgen, Ronald P. Stolk, Weihua Zhang, Smith Av, Cornelia M. van Duijn, Bernhard R. Winkelmann, Brown Mj, Susan Campbell, Brenda W. Penninx, Olivier Devuyst, Gaffo Al, Johannes H. Smit, Ivana Kolcic, Zhao Jh, Robert M. Plenge, Nicholas Hastie, Laura Portas, Feitosa Mf, Ivana Persico, Beverley Balkau, Philippe Froguel, James F. Wilson, Tõnu Esko

, Lopez Lm, Kay Tee Khaw, Kleber Me, Claudia Langenberg, Halit Ongen, Aaron Isaacs, Hicks Aa, Fernando Rivadeneira, Aldi Kraja, Nolte Im, Andre G. Uitterlinden, Elizabeth G. Holliday, Ramaiah Nagaraja, Peden Jf, Maria Grazia Piras, Stefania Bandinelli, Matthias Nauck, A. Kottgen, Jeffrey E. Metter, Claudia Schurmann

, Antonio Lupo, Rose Lm, Angela Döring, Eva Lattka, Evropi Theodoratou, Christian Mueller, Inga Prokopenko

, Thun Ga, Michael Stumvoll, Gislason Gk, Markus Perola, Gail Davies, Alan J. Gow, Veikko Salomaa, Marcel Bruinenberg, Launer Lj, So-Youn Shin, Tim D. Spector, Jaspal S. Kooner, Shuldiner Ar, Cinzia Sala, Paul M. Ridker, Bernhard O. Boehm, Montgomery Gw, Jorma Viikari, Susanne Lucae, Christopher P. Nelson, O'Seaghdha Cm, Michael A. Nalls, Gary Curhan, Pankaj Sharma, Poorva Mudgal, Andrew B. Singleton, Jacobs Dr, Rotter Ji, C. M. Van Duijn, Tanja Zeller, Psaty Bm, Mirna Kirin, Irene Mateo Leach, Khaw Kt, Pio D’Adamo, Anuj Goel, Mario Pirastu, Albert Hofman, Silvia Tore, Nicole M. Probst-Hensch, Medea Imboden, Holliday Eg, Henry Völzke, Metter Je, Francesco Cucca, Afshin Parsa, Wichmann He, Reinhold Schmidt, Kathrin Budde, John B. Whitfield, Florian Ernst, Gow Aj, Susan M. Farrington, Johnson Ad, David S. Siscovick, Ozren Polasek, Angela Doering, Antti Jula, Igor Rudan

, H. Erich Wichmann, Mika Kähönen, Christian Hengstenberg, Kooner Js, James F. Meschia, Bruce H. R. Wolffenbuttel, Winkelmann Br, Winfried März, Boehm Bo, Naoyuki Kamatani, Peter Pp Pramstaller

, Michel Burnier, Penninx Bw, Harold Snieder, Smit Jh, John Attia, Maris Laan

, Wilson Jf, Alan F. Wright, Leach Im, Norman Klopp, Gerjan Navis, Hans L. Hillege, Uitterlinden Ag, Stefan Kloiber, Hugh Watkins, Irene Mateo Leach, Hyon Choi, Jacqueline C. M. Witteman, Piras Mg, Serena Sanna

, Sabine Schipf, Vilmundur Gudnason, Nelson Cp, Anke Tönjes, Mika Kaehoenen, Samuli Ripatti, Myriam Fornage, Nicole Soranzo, Meschia Jf, Paolo Gasparini, Daniela Toniolo, Nalls Ma, Harry Campbell, Singleton Ab, Olli Raitakari, Hillege Hl, Nabila Bouatia-Naji, Whitfield Jb, Andres Metspalu, Ruth J. F. Loos, Siscovick Ds, van Duijn Cm, Ingrid B. Borecki, Consortium Diagram, Luigi Ferrucci, Giovanni Gambaro, Borecki Ib, Ian J. Deary, Consortium Icbp, Deary Ij, John C. Chambers, Wolffenbuttel Bh, Ulf Gyllensten, Consortium Magic, Winfried Maerz, Chambers Jc, CARDIoGRAM Consortium, Malcolm G. Dunlop, Mika Kahonen, Wright Af, Witteman Jc, Dunlop Mg, Winfried März, Daniel I. Chasman, Chasman Di, Wh H. Linda Kao, Marina Ciullo, Caroline S. Fox, Fox Cs, Mark Caulfield, Murielle Bochud, W. H. Linda Kao, Christian Gieger

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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.

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

Abstract