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

LifeLines Cohort Study, Anna Köttgen, 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 BrownAngelo 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, Sarah H Wild, Albert Tenesa, Pau Navarro, Nicholas Hastie, Gail Davies, Alan J Gow, James F Wilson, Susan M Farrington, Evropi Theodoratou, Ozren Polasek, Harry Campbell, Igor Rudan, Ian J Deary, Alan F Wright, Malcolm G Dunlop

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.
Original languageEnglish
Pages (from-to)145-154
Number of pages10
JournalNature Genetics
Volume45
Issue number2
DOIs
Publication statusPublished - Feb 2013

Fingerprint

Dive into the research topics of 'Genome-wide association analyses identify 18 new loci associated with serum urate concentrations'. Together they form a unique fingerprint.

Cite this