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

Koettgen, 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, Zoltan, 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., Lehtimaki, Terho, Woodward, Owen M., Okada, Yukinori, Tin, Adrienne, Mueller, 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., Jr., 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, Tonu, 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, Doering, 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., Kaehoenen, 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., Voelzke, Henry, Gudnason, Vilmundur, Parsa, Afshin, Schmidt, Reinhold, Whitfield, John B., Fornage, Myriam, Gasparini, Paolo, Siscovick, David S., Polasek, 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., Maerz, 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., Toenjes, 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 and Gieger, Christian (2013) Genome-wide association analyses identify 18 new loci associated with serum urate concentrations. Nature Genetics, 45 2: 145-154. doi:10.1038/ng.2500


Author Koettgen, 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, Zoltan
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.
Lehtimaki, Terho
Woodward, Owen M.
Okada, Yukinori
Tin, Adrienne
Mueller, 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., Jr.
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, Tonu
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
Doering, 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.
Kaehoenen, 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.
Voelzke, Henry
Gudnason, Vilmundur
Parsa, Afshin
Schmidt, Reinhold
Whitfield, John B.
Fornage, Myriam
Gasparini, Paolo
Siscovick, David S.
Polasek, 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.
Maerz, 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.
Toenjes, 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
Title Genome-wide association analyses identify 18 new loci associated with serum urate concentrations
Journal name Nature Genetics   Check publisher's open access policy
ISSN 1546-1718
1061-4036
Publication date 2013-02-01
Year available 2013
Sub-type Article (original research)
DOI 10.1038/ng.2500
Open Access Status Not yet assessed
Volume 45
Issue 2
Start page 145
End page 154
Total pages 10
Place of publication New York, United States
Publisher Nature Publishing Group
Language eng
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, SEMBT1, 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.
Formatted 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.
Keyword Genetics & Heredity
Genetics & Heredity
GENETICS & HEREDITY
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID BB/F019394/1
12076
CZB/4/710
Z01 AG000954-06
G0401527
UL1 TR000124
P01 CA087969
K12 RR023250
U01 HG004402
HHSN268201100005C
R01 AG020098
K05 AA017688
P60 AR047785
R01 DA012854
P30 DK063491
U01 GM074518
R01 MH066206
090532
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
 
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