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

A. Kottgen; E. Albrecht; A. Teumer; V. Vitart; J. Krumsiek; C. Hundertmark; G. Pistis; D. Ruggiero; C.M. O'Seaghdha; T. Haller; Q. Yang; A.D. Johnson; Z. Kutalik; A.V. Smith; J.L. Shi; M. Struchalin; R.P.S. Middelberg; M.J. Brown; A.L. Gaffo; N. Pirastu; G. Li; C. Hayward; T. Zemunik; J. Huffman; L. Yengo; J.H. Zhao; A. Demirkan; M.F. Feitosa; X. Liu; G. Malerba; L.M. Lopez; P. van der Harst; X.Z. Li; M.E. Kleber; A.A. Hicks; I.M. Nolte; A. Johansson; F. Murgia; S.H. Wild; S.J.L. Bakker; J.F. Peden; A. Dehghan; M. Steri; A. Tenesa; V. Lagou; P. Salo; M. Mangino; L.M. Rose; T. Lehtimaki; O.M. Woodward; Y. Okada; A. Tin; C. Muller; C. Oldmeadow; M. Putku; D. Czamara; P. Kraft; L. Frogheri; G.A. Thun; A. Grotevendt; G.K. Gislason; T.B. Harris; L.J. Launer; P. McArdle; A.R. Shuldiner; E. Boerwinkle; J. Coresh; H. Schmidt; M. Schallert; N.G. Martin; G.W. Montgomery; M. Kubo; Y. Nakamura; T. Tanaka; P.B. Munroe; N.J. Samani; D.R. Jacobs; K. Liu; P. d'Adamo; S. Ulivi; J.I. Rotter; B.M. Psaty; P. Vollenweider; G. Waeber; S. Campbell; O. Devuyst; P. Navarro; I. Kolcic; N. Hastie; B. Balkau; P. Froguel; T. Esko; A. Salumets; K.T. Khaw; C. Langenberg; N.J. Wareham; A. Isaacs; A. Kraja; Q.Y. Zhang; B.W.J.H. Penninx; J.H. Smit; M. Bochud; C. Gieger

doi:10.1038/ng.2500

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

A. Kottgen, E. Albrecht, A. Teumer, V. Vitart, J. Krumsiek, C. Hundertmark, G. Pistis, D. Ruggiero, C.M. O'Seaghdha, T. Haller, Q. Yang, A.D. Johnson, Z. Kutalik, A.V. Smith, J.L. Shi, M. Struchalin, R.P.S. Middelberg, M.J. Brown, A.L. Gaffo, N. PirastuG. Li, C. Hayward, T. Zemunik, J. Huffman, L. Yengo, J.H. Zhao, A. Demirkan, M.F. Feitosa, X. Liu, G. Malerba, L.M. Lopez, P. van der Harst, X.Z. Li, M.E. Kleber, A.A. Hicks, I.M. Nolte, A. Johansson, F. Murgia, S.H. Wild, S.J.L. Bakker, J.F. Peden, A. Dehghan, M. Steri, A. Tenesa, V. Lagou, P. Salo, M. Mangino, L.M. Rose, T. Lehtimaki, O.M. Woodward, Y. Okada, A. Tin, C. Muller, C. Oldmeadow, M. Putku, D. Czamara, P. Kraft, L. Frogheri, G.A. Thun, A. Grotevendt, G.K. Gislason, T.B. Harris, L.J. Launer, P. McArdle, A.R. Shuldiner, E. Boerwinkle, J. Coresh, H. Schmidt, M. Schallert, N.G. Martin, G.W. Montgomery, M. Kubo, Y. Nakamura, T. Tanaka, P.B. Munroe, N.J. Samani, D.R. Jacobs, K. Liu, P. d'Adamo, S. Ulivi, J.I. Rotter, B.M. Psaty, P. Vollenweider, G. Waeber, S. Campbell, O. Devuyst, P. Navarro, I. Kolcic, N. Hastie, B. Balkau, P. Froguel, T. Esko, A. Salumets, K.T. Khaw, C. Langenberg, N.J. Wareham, A. Isaacs, A. Kraja, Q.Y. Zhang, B.W.J.H. Penninx, J.H. Smit, M. Bochud, C. Gieger

Research output: Contribution to Journal › Article › Academic › peer-review

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. © 2013 Nature America, Inc. All rights reserved.

Original language	English
Pages (from-to)	145-154
Journal	Nature Genetics
Volume	45
Issue number	2
DOIs	https://doi.org/10.1038/ng.2500
Publication status	Published - 2013

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Kottgen, A., Albrecht, E., Teumer, A., Vitart, V., Krumsiek, J., Hundertmark, C., Pistis, G., Ruggiero, D., O'Seaghdha, C. M., Haller, T., Yang, Q., Johnson, A. D., Kutalik, Z., Smith, A. V., Shi, J. L., Struchalin, M., Middelberg, R. P. S., Brown, M. J., Gaffo, A. L., ... 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

@article{69ff49cd4d80476e8410e13524f253d7,

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. {\textcopyright} 2013 Nature America, Inc. All rights reserved.",

author = "A. Kottgen and E. Albrecht and A. Teumer and V. Vitart and J. Krumsiek and C. Hundertmark and G. Pistis and D. Ruggiero and C.M. O'Seaghdha and T. Haller and Q. Yang and A.D. Johnson and Z. Kutalik and A.V. Smith and J.L. Shi and M. Struchalin and R.P.S. Middelberg and M.J. Brown and A.L. Gaffo and N. Pirastu and G. Li and C. Hayward and T. Zemunik and J. Huffman and L. Yengo and J.H. Zhao and A. Demirkan and M.F. Feitosa and X. Liu and G. Malerba and L.M. Lopez and {van der Harst}, P. and X.Z. Li and M.E. Kleber and A.A. Hicks and I.M. Nolte and A. Johansson and F. Murgia and S.H. Wild and S.J.L. Bakker and J.F. Peden and A. Dehghan and M. Steri and A. Tenesa and V. Lagou and P. Salo and M. Mangino and L.M. Rose and T. Lehtimaki and O.M. Woodward and Y. Okada and A. Tin and C. Muller and C. Oldmeadow and M. Putku and D. Czamara and P. Kraft and L. Frogheri and G.A. Thun and A. Grotevendt and G.K. Gislason and T.B. Harris and L.J. Launer and P. McArdle and A.R. Shuldiner and E. Boerwinkle and J. Coresh and H. Schmidt and M. Schallert and N.G. Martin and G.W. Montgomery and M. Kubo and Y. Nakamura and T. Tanaka and P.B. Munroe and N.J. Samani and D.R. Jacobs and K. Liu and P. d'Adamo and S. Ulivi and J.I. Rotter and B.M. Psaty and P. Vollenweider and G. Waeber and S. Campbell and O. Devuyst and P. Navarro and I. Kolcic and N. Hastie and B. Balkau and P. Froguel and T. Esko and A. Salumets and K.T. Khaw and C. Langenberg and N.J. Wareham and A. Isaacs and A. Kraja and Q.Y. Zhang and B.W.J.H. Penninx and J.H. Smit and M. Bochud and C. Gieger",

year = "2013",

doi = "10.1038/ng.2500",

language = "English",

volume = "45",

pages = "145--154",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "2",

}

Kottgen, A, Albrecht, E, Teumer, A, Vitart, V, Krumsiek, J, Hundertmark, C, Pistis, G, Ruggiero, D, O'Seaghdha, CM, Haller, T, Yang, Q, Johnson, AD, Kutalik, Z, Smith, AV, Shi, JL, 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, XZ, 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, Lehtimaki, T, Woodward, OM, Okada, Y, Tin, A, Muller, 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, QY, Penninx, BWJH, Smit, JH, 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

TY - JOUR

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

AU - Kottgen, A.

AU - Albrecht, E.

AU - Teumer, A.

AU - Vitart, V.

AU - Krumsiek, J.

AU - Hundertmark, C.

AU - Pistis, G.

AU - Ruggiero, D.

AU - O'Seaghdha, C.M.

AU - Haller, T.

AU - Yang, Q.

AU - Johnson, A.D.

AU - Kutalik, Z.

AU - Smith, A.V.

AU - Shi, J.L.

AU - Struchalin, M.

AU - Middelberg, R.P.S.

AU - Brown, M.J.

AU - Gaffo, A.L.

AU - Pirastu, N.

AU - Li, G.

AU - Hayward, C.

AU - Zemunik, T.

AU - Huffman, J.

AU - Yengo, L.

AU - Zhao, J.H.

AU - Demirkan, A.

AU - Feitosa, M.F.

AU - Liu, X.

AU - Malerba, G.

AU - Lopez, L.M.

AU - van der Harst, P.

AU - Li, X.Z.

AU - Kleber, M.E.

AU - Hicks, A.A.

AU - Nolte, I.M.

AU - Johansson, A.

AU - Murgia, F.

AU - Wild, S.H.

AU - Bakker, S.J.L.

AU - Peden, J.F.

AU - Dehghan, A.

AU - Steri, M.

AU - Tenesa, A.

AU - Lagou, V.

AU - Salo, P.

AU - Mangino, M.

AU - Rose, L.M.

AU - Lehtimaki, T.

AU - Woodward, O.M.

AU - Okada, Y.

AU - Tin, A.

AU - Muller, C.

AU - Oldmeadow, C.

AU - Putku, M.

AU - Czamara, D.

AU - Kraft, P.

AU - Frogheri, L.

AU - Thun, G.A.

AU - Grotevendt, A.

AU - Gislason, G.K.

AU - Harris, T.B.

AU - Launer, L.J.

AU - McArdle, P.

AU - Shuldiner, A.R.

AU - Boerwinkle, E.

AU - Coresh, J.

AU - Schmidt, H.

AU - Schallert, M.

AU - Martin, N.G.

AU - Montgomery, G.W.

AU - Kubo, M.

AU - Nakamura, Y.

AU - Tanaka, T.

AU - Munroe, P.B.

AU - Samani, N.J.

AU - Jacobs, D.R.

AU - Liu, K.

AU - d'Adamo, P.

AU - Ulivi, S.

AU - Rotter, J.I.

AU - Psaty, B.M.

AU - Vollenweider, P.

AU - Waeber, G.

AU - Campbell, S.

AU - Devuyst, O.

AU - Navarro, P.

AU - Kolcic, I.

AU - Hastie, N.

AU - Balkau, B.

AU - Froguel, P.

AU - Esko, T.

AU - Salumets, A.

AU - Khaw, K.T.

AU - Langenberg, C.

AU - Wareham, N.J.

AU - Isaacs, A.

AU - Kraja, A.

AU - Zhang, Q.Y.

AU - Penninx, B.W.J.H.

AU - Smit, J.H.

AU - Bochud, M.

AU - Gieger, C.

PY - 2013

Y1 - 2013

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. © 2013 Nature America, Inc. All rights reserved.

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. © 2013 Nature America, Inc. All rights reserved.

U2 - 10.1038/ng.2500

DO - 10.1038/ng.2500

M3 - Article

SN - 1061-4036

VL - 45

SP - 145

EP - 154

JO - Nature Genetics

JF - Nature Genetics

IS - 2

ER -

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

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