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

TitleGenome-wide association analyses identify 18 new loci associated with serum urate concentrations.
Publication TypeJournal Article
Year of Publication2013
AuthorsKöttgen, 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, GAndri, Grotevendt, A, Gislason, GKjartan, 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, KTee, 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, H-E, 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, IMateo, van Gilst, WH, Goel, A, Ongen, H, Hofman, A, Rivadeneira, F, Uitterlinden, AG, Imboden, M, von Eckardstein, A, Cucca, F, Nagaraja, R, Piras, MGrazia, Nauck, M, Schurmann, C, Budde, K, Ernst, F, Farrington, SM, Theodoratou, E, Prokopenko, I, Stumvoll, M, Jula, A, Perola, M, Salomaa, V, Shin, S-Y, 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, Polasek, 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, LWH, Ciullo, M, Fox, CS, Caulfield, M, Bochud, M, Gieger, C
Corporate/Institutional AuthorsLifeLines Cohort Study,, CARDIoGRAM consortium, DIAGRAM Consortium, ICBP Consortium,, MAGIC Consortium,
JournalNat Genet
Volume45
Issue2
Pagination145-54
Date Published2013 Feb
ISSN1546-1718
KeywordsAnalysis of Variance, European Continental Ancestry Group, Gene Frequency, Genetic Loci, Genome-Wide Association Study, Glucose, Gout, Humans, Inhibins, Polymorphism, Single Nucleotide, Signal Transduction, Uric Acid
Abstract<p>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.</p>
DOI10.1038/ng.2500
Alternate JournalNat. Genet.
PubMed ID23263486
PubMed Central IDPMC3663712
Grant ListHHSN268201100012C / HL / NHLBI NIH HHS / United States
CZB/4/710 / / Chief Scientist Office / United Kingdom
G9521010 / / Medical Research Council / United Kingdom
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K12 RR023250 / RR / NCRR NIH HHS / United States
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MR/K026992/1 / / Medical Research Council / United Kingdom
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MC_PC_U127592696 / / Medical Research Council / United Kingdom
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