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

LifeLines Cohort Study, CARDIoGRAM Consortium, DIAGRAM Consortium, ICBP Consortium, MAGIC Consortium

    Research output: Contribution to journalArticle

    398 Citations (Scopus)

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

    Keywords

    • Uric Acid
    • Polymorphism, Single Nucleotide
    • Analysis of Variance
    • Genetic Loci
    • Gene Frequency
    • Humans
    • European Continental Ancestry Group
    • Glucose
    • Inhibins
    • Signal Transduction
    • Gout
    • Genome-Wide Association Study

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