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

Authors :
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
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
Publication Year :
2013

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.

Details

Database :
OAIster
Notes :
text, Köttgen, Anna and Albrecht, Eva and Teumer, Alexander and Vitart, Veronique and Krumsiek, Jan and Hundertmark, Claudia and Pistis, Giorgio and Ruggiero, Daniela and O'Seaghdha, Conall M and Haller, Toomas and Yang, Qiong and Tanaka, Toshiko and Johnson, Andrew D and Kutalik, Zoltán and Smith, Albert V and Shi, Julia and Struchalin, Maksim and Middelberg, Rita P S and Brown, Morris J and Gaffo, Angelo L and Pirastu, Nicola and Li, Guo and Hayward, Caroline and Zemunik, Tatijana and Huffman, Jennifer and Yengo, Loic and Zhao, Jing Hua and Demirkan, Ayse and Feitosa, Mary F and Liu, Xuan and Malerba, Giovanni and Lopez, Lorna M. and van der Harst, Pim and Li, Xinzhong and Kleber, Marcus E and Hicks, Andrew A and Nolte, Ilja M and Johansson, Asa and Murgia, Federico and Wild, Sarah H and Bakker, Stephan J L and Peden, John F and Dehghan, Abbas and Steri, Maristella and Tenesa, Albert and Lagou, Vasiliki and Salo, Perttu and Mangino, Massimo and Rose, Lynda M and Lehtimäki, Terho and Woodward, Owen M and Okada, Yukinori and Tin, Adrienne and Müller, Christian and Oldmeadow, Christopher and Putku, Margus and Czamara, Darina and Kraft, Peter and Frogheri, Laura and Thun, Gian Andri and Grotevendt, Anne and Gislason, Gauti Kjartan and Harris, Tamara B and Launer, Lenore J and McArdle, Patrick and Shuldiner, Alan R and Boerwinkle, Eric and Coresh, Josef and Schmidt, Helena and Schallert, Michael and Martin, Nicholas G and Montgomery, Grant W and Kubo, Michiaki and Nakamura, Yusuke and Tanaka, Toshihiro and Munroe, Patricia B and Samani, Nilesh J and Jacobs, David R and Liu, Kiang and D'Adamo, Pio and Ulivi, Sheila and Rotter, Jerome I and Psaty, Bruce M and Vollenweider, Peter and Waeber, Gerard and Campbell, Susan and Devuyst, Olivier and Navarro, Pau and Kolcic, Ivana and Hastie, Nicholas and Balkau, Beverley and Froguel, Philippe and Esko, Tõnu and Salumets, Andres and Khaw, Kay Tee and Langenberg, Claudia and Wareham, Nicholas J and Isaacs, Aaron and Kraja, Aldi and Zhan, English
Publication Type :
Electronic Resource
Accession number :
edsoai.on1388614281
Document Type :
Electronic Resource