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Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma

Chambers, John C
Zhang, Weihua
Sehmi, Joban
Li, Xinzhong
Wass, Mark N
Van der Harst, Pim
Holm, Hilma
Sanna, Serena
show hidden authors show all authors [1 - 9]
CollaborationWith : Ehret, Georg Benedikt
Published in Nature genetics. 2011, vol. 43, no. 11, p. 1131-8
Abstract Concentrations of liver enzymes in plasma are widely used as indicators of liver disease. We carried out a genome-wide association study in 61,089 individuals, identifying 42 loci associated with concentrations of liver enzymes in plasma, of which 32 are new associations (P = 10(-8) to P = 10(-190)). We used functional genomic approaches including metabonomic profiling and gene expression analyses to identify probable candidate genes at these regions. We identified 69 candidate genes, including genes involved in biliary transport (ATP8B1 and ABCB11), glucose, carbohydrate and lipid metabolism (FADS1, FADS2, GCKR, JMJD1C, HNF1A, MLXIPL, PNPLA3, PPP1R3B, SLC2A2 and TRIB1), glycoprotein biosynthesis and cell surface glycobiology (ABO, ASGR1, FUT2, GPLD1 and ST3GAL4), inflammation and immunity (CD276, CDH6, GCKR, HNF1A, HPR, ITGA1, RORA and STAT4) and glutathione metabolism (GSTT1, GSTT2 and GGT), as well as several genes of uncertain or unknown function (including ABHD12, EFHD1, EFNA1, EPHA2, MICAL3 and ZNF827). Our results provide new insight into genetic mechanisms and pathways influencing markers of liver function.
Keywords Enzymes/blood/geneticsGenome-Wide Association StudyHumansLiver/enzymologyPolymorphism, Single Nucleotide
PMID: 22001757
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Research group Traits génétiques complexes (901)
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CHAMBERS, John C et al. Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma. In: Nature genetics, 2011, vol. 43, n° 11, p. 1131-8. doi: 10.1038/ng.970 https://archive-ouverte.unige.ch/unige:32742

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Deposited on : 2014-01-02

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