Open Access
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,Zoltán 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 E. 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,Åsa 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 Lehtimäki,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 F. 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,Gérard Waeber,Susan Campbell,Olivier Devuyst,Pau Navarro,Ivana Kolcic,Nicholas D. Hastie,Beverley Balkau,Philippe Froguel,Tõnu Esko,Andres Salumets,Kay-Tee Khaw,Claudia Langenberg,Nicholas J. Wareham,Aaron Isaacs,Aldi T. Kraja,Qunyuan Zhang,Philipp S. Wild,Rodney J. Scott,Elizabeth G. Holliday,Elin Org,Margus Viigimaa,Stefania Bandinelli,Jeffrey Metter,Antonio Lupo,Elisabetta Trabetti,Rossella Sorice,Angela Doering,Eva Lattka,Konstantin Strauch,Fabian J. Theis,Melanie Waldenberger,H-Erich Wichmann,Gail Davies,Alan J. Gow,Marcel Bruinenberg,Ronald P. Stolk,Jaspal S. Kooner,Weihua Zhang,Bernhard R. Winkelmann,Bernhard O. Boehm,Susanne Lucae,Brenda W.J.H. Penninx,Johannes H. Smit,Gary C. Curhan,Poorva Mudgal,Robert M. Plenge,Laura Portas,Ivana Persico,Mirna Kirin,James F. Wilson,Irene Mateo Leach,Wiek H. van Gilst,Anuj Goel,Halit Ongen,Albert Hofman,Fernando Rivadeneira,André G. Uitterlinden,Medea Imboden,Arnold von Eckardstein,Francesco Cucca,Ramaiah Nagaraja,Maria Grazia Piras,Matthias Nauck,Claudia Schurmann,Kathrin Budde,Florian Ernst,Susan M. Farrington,Evropi Theodoratou,Inga Prokopenko,Michael Stumvoll,Antti Jula,Markus Perola,Veikko Salomaa,So-Youn Shin,Tim D. Spector,Cinzia Sala,Paul M. Ridker,Mika Kaehoenen,Jorma Viikari,Christian Hengstenberg,Christopher P. Nelson,James F. Meschia,Mike A. Nalls,Pankaj Sharma,Andrew B. Singleton,Naoyuki Kamatani,Tanja Zeller,Michel Burnier,John Attia,Maris Laan,Norman Klopp,Hans L. Hillege,Stefan Kloiber,Hyon K. Choi,Mario Pirastu,Silvia Tore,Nicole Probst-Hensch,Henry Voelzke,Vilmundur Gudnason,Afshin Parsa,Reinhold E. Schmidt,John Whitfield,Myriam Fornage,Paolo Gasparini,David S. Siscovick,Ozren Polasek,Harry Campbell,Igor Rudan,Nabila Bouatia-Naji,Andres Metspalu,Ruth J. F. Loos,Cornelia M. van Duijn,Ingrid B. Borecki,Luigi Ferrucci,Giovanni Gambaro,Ian J. Deary,Bruce H. R. Wolffenbuttel,John C. Chambers,Winfried Maerz,Peter P. Pramstaller,Harold Snieder,Ulf Gyllensten,Alan F. Wright,Gerjan Navis,Hugh Watkins,Jacqueline C.M. Witteman,Serena Sanna,Sabine Schipf,Malcolm G. Dunlop,Anke Toenjes,Samuli Ripatti,Nicole Soranzo,Daniela Toniolo,Daniel I. Chasman,Olli T. Raitakari,W. H. Linda Kao,Marina Ciullo,Caroline S. Fox,Mark J. Caulfield,Murielle Bochud,Christian Gieger +224 more
TLDR
In this article, the authors 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).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.read more
Citations
More filters
Journal ArticleDOI
Modulation of genetic associations with serum urate levels by body-mass-index in humans
Jennifer E. Huffman,Eva Albrecht,Alexander Teumer,Massimo Mangino,Karen Kapur,Toby Johnson,Z. Kutalik,Nicola Pirastu,Giorgio Pistis,Lorna M. Lopez,Toomas Haller,Perttu Salo,Anuj Goel,Man Li,Toshiko Tanaka,Abbas Dehghan,Daniela Ruggiero,Giovanni Malerba,Albert V. Smith,Ilja M. Nolte,Laura Portas,Amanda Phipps-Green,Lora Boteva,Pau Navarro,Åsa Johansson,Andrew A. Hicks,Ozren Polasek,Tõnu Esko,John F. Peden,Sarah E. Harris,Federico Murgia,Sarah H. Wild,Albert Tenesa,Adrienne Tin,Evelin Mihailov,Anne Grotevendt,Gauti Kjartan Gislason,Josef Coresh,Pio D'Adamo,Sheila Ulivi,Peter Vollenweider,Gérard Waeber,Susan Campbell,Ivana Kolcic,Krista Fisher,Margus Viigimaa,Jeffrey Metter,Corrado Masciullo,Elisabetta Trabetti,Cristina Bombieri,Rossella Sorice,Angela Doering,Eva Reischl,Konstantin Strauch,Albert Hofman,André G. Uitterlinden,Melanie Waldenberger,H-Erich Wichmann,Gail Davies,Alan J. Gow,Nicola Dalbeth,Lisa K. Stamp,Johannes H. Smit,Mirna Kirin,Ramaiah Nagaraja,Matthias Nauck,Claudia Schurmann,Kathrin Budde,Susan M. Farrington,Evropi Theodoratou,Antti Jula,Veikko Salomaa,Cinzia Sala,Christian Hengstenberg,Michel Burnier,R Maegi,Norman Klopp,Stefan Kloiber,Sabine Schipf,Samuli Ripatti,Stefano Cabras,Nicole Soranzo,Georg Homuth,Teresa Nutile,Patricia B. Munroe,Nicholas D. Hastie,Harry Campbell,Igor Rudan,Claudia P. Cabrera,Chris Haley,Oscar H. Franco,Tony R. Merriman,Vilmundur Gudnason,Mario Pirastu,Brenda W.J.H. Penninx,Brenda W.J.H. Penninx,Harold Snieder,Andres Metspalu,Marina Ciullo,Peter P. Pramstaller,Cornelia M. van Duijn,Luigi Ferrucci,Giovanni Gambaro,Ian J. Deary,Malcolm G. Dunlop,James F. Wilson,Paolo Gasparini,Ulf Gyllensten,Tim D. Spector,Alan F. Wright,Caroline Hayward,Hugh Watkins,Markus Perola,Murielle Bochud,W. H. Linda Kao,Mark J. Caulfield,Daniela Toniolo,Henry Voelzke,Christian Gieger,Anna Koettgen,Veronique Vitart +120 more
TL;DR: Interactions between body mass index (BMI) and common genetic variants affecting serum urate levels, genome-wide, and regression-type analyses in a non BMI-stratified overall sample suggested a role for N-glycan biosynthesis as a prominent urate-associated pathway in the lean stratum.
Journal ArticleDOI
Global epidemiology of gout: prevalence, incidence and risk factors
TL;DR: Data from epidemiological studies from diverse regions of the world are synthesized to depict the geographic variation in gout prevalence and incidence, and indicate that the distribution of gout is uneven across the globe, with prevalence being highest in Pacific countries.
Journal ArticleDOI
SLC transporters as therapeutic targets: emerging opportunities
TL;DR: Current and investigational drugs that modulate SLC transporters, as well as promising drug targets, are highlighted.
Journal ArticleDOI
A catalog of genetic loci associated with kidney function from analyses of a million individuals
TL;DR: Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ and provide a comprehensive priority list of molecular targets for translational research.
References
More filters
Journal ArticleDOI
PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage Analyses
Shaun Purcell,Shaun Purcell,Benjamin M. Neale,Benjamin M. Neale,Kathe Todd-Brown,Lori Thomas,Manuel A. R. Ferreira,David Bender,David Bender,Julian Maller,Julian Maller,Pamela Sklar,Pamela Sklar,Paul I.W. de Bakker,Paul I.W. de Bakker,Mark J. Daly,Mark J. Daly,Pak C. Sham +17 more
TL;DR: This work introduces PLINK, an open-source C/C++ WGAS tool set, and describes the five main domains of function: data management, summary statistics, population stratification, association analysis, and identity-by-descent estimation, which focuses on the estimation and use of identity- by-state and identity/descent information in the context of population-based whole-genome studies.
Journal ArticleDOI
Statistical significance for genomewide studies
John D. Storey,Robert Tibshirani +1 more
TL;DR: This work proposes an approach to measuring statistical significance in genomewide studies based on the concept of the false discovery rate, which offers a sensible balance between the number of true and false positives that is automatically calibrated and easily interpreted.
Journal ArticleDOI
GCTA: a tool for genome-wide complex trait analysis.
TL;DR: The GCTA software is a versatile tool to estimate and partition complex trait variation with large GWAS data sets and focuses on the function of estimating the variance explained by all the SNPs on the X chromosome and testing the hypotheses of dosage compensation.
Journal ArticleDOI
Potential etiologic and functional implications of genome-wide association loci for human diseases and traits
Lucia A. Hindorff,Praveen Sethupathy,Heather Junkins,Erin M. Ramos,Jayashri P. Mehta,Francis S. Collins,Teri A. Manolio +6 more
TL;DR: An online catalog of SNP-trait associations from published genome-wide association studies for use in investigating genomic characteristics of trait/disease-associated SNPs (TASs) is developed, well-suited to guide future investigations of the role of common variants in complex disease etiology.
Journal ArticleDOI
METAL: fast and efficient meta-analysis of genomewide association scans.
TL;DR: METAL provides a computationally efficient tool for meta-analysis of genome-wide association scans, which is a commonly used approach for improving power complex traits gene mapping studies.
Related Papers (5)
Genome-Wide Haplotype Analysis of Cis Expression Quantitative Trait Loci in Monocytes
Sophie Garnier,Vinh Truong,Jessy Brocheton,Tanja Zeller,Maxime Rovital,Philipp S. Wild,Andreas Ziegler,Thomas Münzel,Laurence Tiret,Stefan Blankenberg,Panos Deloukas,J Erdmann,Christian Hengstenberg,Nilesh J. Samani,Nilesh J. Samani,Heribert Schunkert,Willem H. Ouwehand,Willem H. Ouwehand,Alison H. Goodall,Alison H. Goodall,François Cambien,David-Alexandre Trégouët +21 more