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

Autoria(s): Köttgen A.; Albrecht E.; Teumer A.; Vitart V.; Krumsiek J.; Hundertmark C.; Pistis G.; Ruggiero D.; O'Seaghdha C.M.; Haller T.; Yang Q.; Tanaka T.; Johnson A.D.; Kutalik Z.; Smith A.V.; Shi J.; Struchalin M.; Middelberg R.P.; Brown M.J.; Gaffo A.L.; Pirastu N.; Li G.; Hayward C.; Zemunik T.; Huffman J.; Yengo L.; Zhao J.H.; Demirkan A.; Feitosa M.F.; Liu X.; Malerba G.; Lopez L.M.; van der Harst P.; Li X.; Kleber M.E.; Hicks A.A.; Nolte I.M.; Johansson A.; Murgia F.; Wild S.H.; Bakker S.J.; Peden J.F.; Dehghan A.; Steri M.; Tenesa A.; Lagou V.; Salo P.; Mangino M.; Rose L.M.; Lehtimäki T.; Woodward O.M.; Okada Y.; Tin A.; Müller C.; Oldmeadow C.; Putku M.; Czamara D.; Kraft P.; Frogheri L.; Thun G.A.; Grotevendt A.; Gislason G.K.; Harris T.B.; Launer L.J.; McArdle P.; Shuldiner A.R.; Boerwinkle E.; Coresh J.; Schmidt H.; Schallert M.; Martin N.G.; Montgomery G.W.; Kubo M.; Nakamura Y.; Tanaka T.; Munroe P.B.; Samani N.J.; Jacobs D.R.; Liu K.; D'Adamo P.; Ulivi S.; Rotter J.I.; Psaty B.M.; Vollenweider P.; Waeber G.; Campbell S.; Devuyst O.; Navarro P.; Kolcic I.; Hastie N.; Balkau B.; Froguel P.; Esko T.; Salumets A.; Khaw K.T.; Langenberg C.; Wareham N.J.; Isaacs A.; Kraja A.; Zhang Q.; Wild P.S.; Scott R.J.; Holliday E.G.; Org E.; Viigimaa M.; Bandinelli S.; Metter J.E.; Lupo A.; Trabetti E.; Sorice R.; Döring A.; Lattka E.; Strauch K.; Theis F.; Waldenberger M.; Wichmann H.E.; Davies G.; Gow A.J.; Bruinenberg M.; LifeLines Cohort Study; Stolk R.P.; Stolk R.P.; Kooner J.S.; Zhang W.; Winkelmann B.R.; Boehm B.O.; Lucae S.; Penninx B.W.; Smit J.H.; Curhan G.; Mudgal P.; Plenge R.M.; Portas L.; Persico I.; Kirin M.; Wilson J.F.; Mateo Leach I.; van Gilst W.H.; Goel A.; Ongen H.; Hofman A.; Rivadeneira F.; Uitterlinden A.G.; Imboden M.; von Eckardstein A.; Cucca F.; Nagaraja R.; Piras M.G.; Nauck M.; Schurmann C.; Budde K.; Ernst F.; Farrington S.M.; Theodoratou E.; Prokopenko I.; Stumvoll M.; Jula A.; Perola M.; Salomaa V.; Shin S.Y.; Spector T.D.; Sala C.; Ridker P.M.; Kähönen M.; Viikari J.; Hengstenberg C.; Nelson C.P.; CARDIoGRAM Consortium; DIAGRAM Consortium; ICBP Consortium; MAGIC Consortium; Meschia J.F.; Meschia J.F.; Nalls M.A.; Sharma P.; Singleton A.B.; Kamatani N.; Zeller T.; Burnier M.; Attia J.; Laan M.; Klopp N.; Hillege H.L.; Kloiber S.; Choi H.; Pirastu M.; Tore S.; Probst-Hensch N.M.; Völzke H.; Gudnason V.; Parsa A.; Schmidt R.; Whitfield J.B.; Fornage M.; Gasparini P.; Siscovick D.S.; Polašek O.; Campbell H.; Rudan I.; Bouatia-Naji N.; Metspalu A.; Loos R.J.; van Duijn C.M.; Borecki I.B.; Ferrucci L.; Gambaro G.; Deary I.J.; Wolffenbuttel B.H.; Chambers J.C.; März W.; Pramstaller P.P.; Snieder H.; Gyllensten U.; Wright A.F.; Navis G.; Watkins H.; Witteman J.C.; Sanna S.; Schipf S.; Dunlop M.G.; Tönjes A.; Ripatti S.; Soranzo N.; Toniolo D.; Chasman D.I.; Raitakari O.; Kao W.H.; Ciullo M.; Fox C.S.; Caulfield M.; Bochud M.; Gieger C.
Data(s)

2013
Resumo

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.
Identificador

http://serval.unil.ch/?id=serval:BIB_772703318942

isbn:1546-1718 (Electronic)

pmid:23263486

doi:10.1038/ng.2500

isiid:000314333000009
Idioma(s)

en
Fonte

Nature Genetics, vol. 45, no. 2, pp. 145-154
Tipo

info:eu-repo/semantics/article

article
Acesso ao item digital