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

被引：749

作者：

Koettgen, Anna ^{[1
,2
]}

Albrecht, Eva ^{[3
]}

Teumer, Alexander ^{[4
]}

Vitart, Veronique ^{[5
]}

Krumsiek, Jan ^{[6
]}

Hundertmark, Claudia ^{[1
]}

Pistis, Giorgio ^{[7
]}

Ruggiero, Daniela ^{[8
]}

O'Seaghdha, Conall M. ^{[9
,10
,11
]}

Haller, Toomas ^{[12
]}

Yang, Qiong ^{[9
,10
,13
]}

Tanaka, Toshiko ^{[14
]}

Johnson, Andrew D. ^{[9
,10
]}

Kutalik, Zoltan ^{[15
,16
]}

Smith, Albert V. ^{[17
,18
]}

Shi, Julia ^{[19
]}

Struchalin, Maksim ^{[20
]}

Middelberg, Rita P. S. ^{[21
,22
]}

Brown, Morris J. ^{[23
]}

Gaffo, Angelo L. ^{[24
,25
]}

Pirastu, Nicola ^{[26
]}

Li, Guo ^{[27
]}

Hayward, Caroline ^{[5
]}

Zemunik, Tatijana ^{[28
]}

Huffman, Jennifer ^{[5
]}

Yengo, Loic ^{[29
,30
]}

Zhao, Jing Hua ^{[31
]}

Demirkan, Ayse ^{[32
]}

Feitosa, Mary F. ^{[33
]}

Liu, Xuan ^{[13
]}

Malerba, Giovanni ^{[34
]}

Lopez, Lorna M. ^{[35
,36
]}

van der Harst, Pim ^{[37
]}

Li, Xinzhong ^{[38
]}

Kleber, Marcus E. ^{[39
,40
]}

Hicks, Andrew A. ^{[41
,42
]}

Nolte, Ilja M. ^{[43
]}

Johansson, Asa ^{[44
,45
]}

Murgia, Federico ^{[46
]}

Wild, Sarah H. ^{[47
]}

Bakker, Stephan J. L. ^{[48
]}

Peden, John F. ^{[49
]}

Dehghan, Abbas ^{[20
]}

Steri, Maristella ^{[50
]}

Tenesa, Albert ^{[5
,51
]}

Lagou, Vasiliki ^{[52
,53
]}

Salo, Perttu ^{[54
]}

Mangino, Massimo ^{[55
]}

Rose, Lynda M. ^{[56
]}

Lehtimaki, Terho ^{[57
,58
]}

机构：

[1] Freiburg Univ Hosp, Renal Div, Freiburg, Germany

[2] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA

[3] Helmholtz Zentrum Munchen, Inst Genet Epidemiol, German Res Ctr Environm Hlth, Neuherberg, Germany

[4] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany

[5] Univ Edinburgh, Med Res Council MRC Human Genet Unit, MRC Inst Genet & Mol Med IGMM, Edinburgh, Midlothian, Scotland

[6] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Bioinformat & Syst Biol, Neuherberg, Germany

[7] Ist Sci San Raffaele, Div Genet & Cell Biol, I-20132 Milan, Italy

[8] CNR, Inst Genet & Biophys A Buzzati Traverso, I-80125 Naples, Italy

[9] NHLBI, Framingham Heart Study, Framingham, MA USA

[10] NHLBI, Ctr Populat Studies, Framingham, MA USA

[11] Massachusetts Gen Hosp, Div Renal, Boston, MA 02114 USA

[12] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia

[13] Boston Univ, Dept Biostat, Boston, MA 02215 USA

[14] NIA, Clin Res Branch, Baltimore, MD 21224 USA

[15] Univ Lausanne, Dept Med Genet, Lausanne, Switzerland

[16] Swiss Inst Bioinformat, Lausanne, Switzerland

[17] Iceland Heart Assoc Res Inst, Kopavogur, Iceland

[18] Univ Iceland, Fac Med, Reykjavik, Iceland

[19] Univ Maryland, Sch Med, Baltimore, MD 21201 USA

[20] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands

[21] Prince Charles Hosp, Dept Med, Chermside, Qld, Australia

[22] Queensland Inst Med Res, Brisbane, Qld 4006, Australia

[23] Univ Cambridge, Clin Pharmacol Unit, Cambridge, England

[24] Univ Alabama Birmingham, Div Rheumatol, Birmingham, AL USA

[25] Univ Alabama Birmingham, Birmingham Vet Affairs Med Ctr, Birmingham, AL USA

[26] Univ Trieste, Inst Maternal & Child Hlth, Ist Ricovero & Cura Carattere Sci IRCCS Burlo Gar, Trieste, Italy

[27] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA

[28] Univ Split, Fac Med, Split, Croatia

[29] Inst Pasteur, CNRS, UMR Genom & Mol Physiol Metab Dis 8199, F-59019 Lille, France

[30] Univ Lille 1, Model Data Anal & Learning MODAL Team, Inst Natl Rech Informat & Automat INRIA Lille Nor, CNRS,UMR 8524,Lab Math, Lille, France

[31] Addenbrookes Hosp, MRC Epidemiol Unit, Inst Metab Sci, Cambridge, England

[32] Erasmus MC, Dept Epidemiol, Subdiv Genet Epidemiol, Rotterdam, Netherlands

[33] Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA

[34] Univ Verona, Biol & Genet Sect, Dept Life & Reprod Sci, I-37100 Verona, Italy

[35] Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland

[36] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland

[37] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands

[38] Univ London Imperial Coll Sci Technol & Med, Inst Clin Sci, Fac Med, London, England

[39] Ludwigshafen Risk & Cardiovasc Hlth LURIC, Freiburg, Germany

[40] Heidelberg Univ, Mannheim Inst Publ Hlth Social & Prevent Med, Med Fac Mannheim, Mannheim, Germany

[41] European Acad Bozen Bolzano EURAC, Ctr Biomed, Bolzano, Italy

[42] Med Univ Lubeck, Affiliated Inst, Lubeck, Germany

[43] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands

[44] Univ Uppsala Hosp, Uppsala Clin Res Ctr, Uppsala, Sweden

[45] Uppsala Univ, Dept Immunol Genet & Pathol, Rudbeck Lab, Uppsala, Sweden

[46] CNR, Inst Populat Genet, Sassari, Italy

[47] Univ Edinburgh, Sch Med, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland

[48] Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, Groningen, Netherlands

[49] Univ Oxford, Wellcome Trust Ctr Human Genet, Dept Cardiovasc Med, Oxford, England

[50] CNR, Ist Ric Genet & Biomed, Monserrato, Italy

来源：

NATURE GENETICS | 2013年 / 45卷 / 02期

基金：

英国惠康基金; 英国生物技术与生命科学研究理事会; 英国医学研究理事会;

关键词：

URIC-ACID CONCENTRATIONS; MOLECULAR PHYSIOLOGY; METABOLIC SYNDROME; GENETIC-LOCI; GOUT; HYPERURICEMIA; RISK; IDENTIFICATION; TRANSPORTER; PREVALENCE;

D O I：

10.1038/ng.2500

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

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.

引用

页码：145 / 154

页数：10

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