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

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

doi:10.1038/ng.2500

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

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

Anna Koettgen, Eva Albrecht, Alexander Teumer, Veronique Vitart, Jan Krumsiek, Claudia Hundertmark, Giorgio Pistis, Daniela Ruggiero, Conall M. O'Seaghdha, Toomas Haller, …

Nature genetics, Vol.45(2), pp.145-154

01/02/2013

DOI: https://doi.org/10.1038/ng.2500

PMID: 23263486

Abstract

Genetics & Heredity

Life Sciences & Biomedicine

Science & Technology

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.

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Title: Genome-wide association analyses identify 18 new loci associated with serum urate concentrations
Creators: Anna Koettgen - Freiburg Univ Hosp, Renal Div, Freiburg, Germany
Eva Albrecht - Helmholtz Zentrum München
Alexander Teumer - Universität Greifswald
Veronique Vitart - MRC Institute of Genetics and Molecular Medicine
Jan Krumsiek - Institute of Bioinformatics and Systems Biology
Claudia Hundertmark - University Medical Center Freiburg
Giorgio Pistis - Mylan
Daniela Ruggiero - Institute of Genetics and Biophysics
Conall M. O'Seaghdha - Framingham Heart Study
Toomas Haller - University of Tartu
Qiong Yang - Framingham Heart Study
Toshiko Tanaka - National Institute on Aging
Andrew D. Johnson - Framingham Heart Study
Zoltan Kutalik - University of Lausanne
Albert V. Smith - Icelandic Heart Association
Julia Shi - University of Maryland, Baltimore
Maksim Struchalin - Erasmus MC
Rita P. S. Middelberg - Prince Charles Hospital
Morris J. Brown - University of Cambridge
Angelo L. Gaffo - University of Alabama at Birmingham
Nicola Pirastu - Istituti di Ricovero e Cura a Carattere Scientifico
Guo Li - University of Washington
Caroline Hayward - MRC Institute of Genetics and Molecular Medicine
Tatijana Zemunik - University of Split
Jennifer Huffman - University of Edinburgh
Loic Yengo - Institut Pasteur de Lille
Jing Hua Zhao - MRC Epidemiology Unit
Ayse Demirkan - Erasmus MC
Mary F. Feitosa - Washington University in St. Louis
Xuan Liu - Boston University
Giovanni Malerba - University of Verona
Lorna M. Lopez - University of Edinburgh
Pim van der Harst - University Medical Center Groningen
Xinzhong Li - University of London
Marcus E. Kleber - Ludwigshafen Risk & Cardiovasc Hlth LURIC, Freiburg, Germany
Andrew A. Hicks - Eurac Research
Ilja M. Nolte - University Medical Center Groningen
Asa Johansson - Uppsala University Hospital
Federico Murgia - CNR, Inst Populat Genet, Sassari, Italy
Sarah H. Wild - University of Edinburgh
Stephan J. L. Bakker - University Medical Center Groningen
John F. Peden - Wellcome Centre for Human Genetics
Abbas Dehghan - Erasmus MC
Maristella Steri - Institute of Genetic and Biomedical Research
Albert Tenesa - MRC Institute of Genetics and Molecular Medicine
Vasiliki Lagou - Oxford Centre for Diabetes, Endocrinology and Metabolism
Perttu Salo - Finnish Institute for Health and Welfare
Massimo Mangino - King's College London
Lynda M. Rose - Brigham and Women's Hospital
Terho Lehtimaki - Fimlab
Owen M. Woodward - Johns Hopkins Medicine
Yukinori Okada - RIKEN Center for Integrative Medical Sciences
Adrienne Tin - Johns Hopkins University
Christian Mueller - Univ Heart Ctr Hamburg, Clin Gen & Intervent Cardiol, Hamburg, Germany
Christopher Oldmeadow - University of Newcastle Australia
Margus Putku - University of Tartu
Darina Czamara - Max Planck Institute of Psychiatry
Peter Kraft - Harvard University
Laura Frogheri - CNR, Inst Populat Genet, Sassari, Italy
Gian Andri Thun - Swiss Tropical and Public Health Institute
Anne Grotevendt - Universitätsmedizin Greifswald
Gauti Kjartan Gislason - Icelandic Heart Association
Tamara B. Harris - National Institute on Aging
Lenore J. Launer - National Institute on Aging
Patrick McArdle - University of Maryland, Baltimore
Alan R. Shuldiner - University of Maryland, Baltimore
Eric Boerwinkle - The University of Texas Health Science Center at Houston
Josef Coresh - Johns Hopkins University
Helena Schmidt - Medical University of Graz
Michael Schallert - Medical University of Graz
Nicholas G. Martin - QIMR Berghofer Medical Research Institute
Grant W. Montgomery - QIMR Berghofer Medical Research Institute
Michiaki Kubo - RIKEN Center for Integrative Medical Sciences
Yusuke Nakamura - The University of Tokyo
Toshihiro Tanaka - RIKEN Center for Integrative Medical Sciences
Patricia B. Munroe - Queen Mary University of London
Nilesh J. Samani - Glenfield Hospital
David R. Jacobs - University of Minnesota
Kiang Liu - Northwestern University
Pio D'Adamo - University of Trieste
Sheila Ulivi - IRCCS Materno Infantile Burlo Garofolo
Jerome I. Rotter - Cedars-Sinai Medical Center
Bruce M. Psaty - University of Washington
Peter Vollenweider - University of Lausanne
Gerard Waeber - University of Lausanne
Susan Campbell - University of Edinburgh
Olivier Devuyst - University of Zurich
Pau Navarro - MRC Institute of Genetics and Molecular Medicine
Ivana Kolcic - University of Split
Nicholas Hastie - MRC Institute of Genetics and Molecular Medicine
Beverley Balkau - Univ Paris 11, Unite Mixte Rech Sante UMRS 1018, Villejuif, France
Philippe Froguel - Institut Pasteur de Lille
Tonu Esko - University of Tartu
Andres Salumets - University of Tartu
Kay Tee Khaw - Addenbrookes Hosp, Clin Gerontol Unit, Cambridge, England
Claudia Langenberg - MRC Epidemiology Unit
Nicholas J. Wareham - Addenbrooke's Hospital
Aaron Isaacs - Erasmus MC
Aldi Kraja - Washington University in St. Louis
Qunyuan Zhang - Washington University in St. Louis
DIAGRAM Consortium
Inga Prokopenko - School of Biosciences
Publication Details: Nature genetics, Vol.45(2), pp.145-154
Publisher: Springer Nature
Number of pages: 10
Date published: 01/02/2013
Grant note: ZIAAG000965 / NATIONAL INSTITUTE ON AGING; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA) K05 AA017688; R01 AA013321; R01 AA007535; R01 AA013326; R01 AA014041; R01 AA013320; P50 AA011998 / NIAAA NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Alcohol Abuse & Alcoholism (NIAAA) R01 AG023629; N01AG12109; R01 AG015928; R01 AG020098; N01AG12100; R01 AG027058; R01 AG018728 / NIA NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA) R01DA012854 / NATIONAL INSTITUTE ON DRUG ABUSE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Drug Abuse (NIDA); European Commission P01 CA087969; R01 CA047988 / NCI NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) UL1TR000124 / NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Advancing Translational Sciences (NCATS) BB/F019394/1 / Biotechnology and Biological Sciences Research Council; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC) MC_U106188470 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) G0801056B / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC); European Commission P30 DK079637; P30 DK072488; P60 DK079637; P30 DK063491 / NIDDK NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK)
Identifiers: 99929050102346
Academic Unit: School of Biosciences; Institute for Sustainability; Surrey Institute for People-Centred AI
Language: English
Resource Type: Journal article

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

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