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

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Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Chambers, JC; Zhang, W; Sehmi, J; Li, X; Wass, MN; Van der Harst, P; Holm, H; Sanna, S; Kavousi, M; Baumeister, SE; Coin, LJ; Deng, G; Gieger, C; Heard-Costa, NL; Hottenga, J-J; Kühnel, B; Kumar, V; Lagou, V; Liang, L; Luan, J; Vidal, PM; Mateo Leach, I; O'Reilly, PF; Peden, JF; Rahmioglu, N; Soininen, P; Speliotes, EK; Yuan, X; Thorleifsson, G; Alizadeh, BZ; Atwood, LD; Borecki, IB; Brown, MJ; Charoen, P; Cucca, F; Das, D; de Geus, EJC; Dixon, AL; Döring, A; Ehret, G; Eyjolfsson, GI; Farrall, M; Forouhi, NG; Friedrich, N; Goessling, W; Gudbjartsson, DF; Harris, TB; Hartikainen, A-L; Heath, S; Hirschfield, GM; Hofman, A; Homuth, G; Hyppönen, E; Janssen, HLA; Johnson, T; Kangas, AJ; Kema, IP; Kühn, JP; Lai, S; Lathrop, M; Lerch, MM; Li, Y; Liang, TJ; Lin, J-P; Loos, RJF; Martin, NG; Moffatt, MF; Montgomery, GW; Munroe, PB; Musunuru, K; Nakamura, Y; O'Donnell, CJ; Olafsson, I; Penninx, BW; Pouta, A; Prins, BP; Prokopenko, I; Puls, R; Ruokonen, A; Savolainen, MJ; Schlessinger, D; Schouten, JNL; Seedorf, U; Sen-Chowdhry, S; Siminovitch, KA; Smit, JH; Spector, TD; Tan, W; Teslovich, TM; Tukiainen, T; Uitterlinden, AG; Van der Klauw, MM; Vasan, RS; Wallace, C; Wallaschofski, H; Wichmann, H-E; Willemsen, G; Würtz, P; Xu, C; Yerges-Armstrong, LM; Alcohol Genome-wide Association (AlcGen) Consortium, ; Diabetes Genetics Replication and Meta-analyses (DIAGRAM+) Study, ; Genetic Investigation of Anthropometric Traits (GIANT) Consortium, ; Global Lipids Genetics Consortium, ; Genetics of Liver Disease (GOLD) Consortium, ; International Consortium for Blood Pressure (ICBP-GWAS), ; Meta-analyses of Glucose and Insulin-Related Traits Consortium (MAGIC), ; Abecasis, GR; Ahmadi, KR; Boomsma, DI; Caulfield, M; Cookson, WO; van Duijn, CM; Froguel, P; Matsuda, K; McCarthy, MI; Meisinger, C; Mooser, V; Pietiläinen, KH; Schumann, G; Snieder, H; Sternberg, MJE; Stolk, RP; Thomas, HC; Thorsteinsdottir, U; Uda, M; Waeber, G; Wareham, NJ; Waterworth, DM; Watkins, H; Whitfield, JB; Witteman, JCM; Wolffenbuttel, BHR; Fox, CS; Ala-Korpela, M; Stefansson, K; Vollenweider, P; Völzke, H; Schadt, EE; Scott, J; Järvelin, M-R; Elliott, P; Kooner, JS

Published Date

  • October 16, 2011

Published In

Volume / Issue

  • 43 / 11

Start / End Page

  • 1131 - 1138

PubMed ID

  • 22001757

Pubmed Central ID

  • 22001757

Electronic International Standard Serial Number (EISSN)

  • 1546-1718

Digital Object Identifier (DOI)

  • 10.1038/ng.970


  • eng

Conference Location

  • United States