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Chambers, J.C.* ; Zhang, W.* ; Sehmi, J.* ; Li, X.* ; Wass, M.N.* ; van der, Harst, P.* ; Holm, H.* ; Sanna, S.* ; Kavousi, M.* ; Baumeister, S.E.* ; Coin, L.J.* ; Deng, G.* ; Gieger, C. ; Heard-Costa, N.L.* ; Hottenga, J.J.* ; Kühnel, B.* ; Kumar, V.* ; Lagou, V.* ; Liang, L.* ; Luan, J.* ; Vidal, P.M.* ; Mateo, Leach, I.* ; O'Reilly, P.F.* ; Peden, J.F.* ; Rahmioglu, N.* ; Soininen, P.* ; Speliotes, E.K.* ; Yuan, X.* ; Thorleifsson, G.* ; Alizadeh, B.Z.* ; Atwood, L.D.* ; Borecki, I.B.* ; Brown, M.J.* ; Charoen, P.* ; Cucca, F.* ; Das, D.* ; de Geus, E.J.* ; Dixon, A.L.* ; Döring, A. ; Ehret, G.* ; Eyjolfsson, G.I.* ; Farrall, M.* ; Forouhi, N.G.* ; Friedrich, N.* ; Goessling, W.* ; Gudbjartsson, D.F.* ; Harris, T.B.* ; Hartikainen, A.L.* ; Heath, S.* ; Hirschfield, G.M.* ; Hofman, A.* ; Homuth, G.* ; Hyppönen, E.* ; Janssen, H.L.* ; Johnson, T.* ; Kangas, A.J.* ; Kema, I.P.* ; Kühn, J.P.* ; Lai, S.* ; Lathrop, M* ; Lerch, M.M.* ; Li, Y.* ; Liang, T.J.* ; Lin, J.P.* ; Loos, R.J.* ; Martin, N.G.* ; Moffatt, M.F.* ; Montgomery, G.W.* ; Munroe, P.B.* ; Musunuru, K.* ; Nakamura, Y.* ; O'Donnell, C.J.* ; Olafsson, I.* ; Penninx, B.W.* ; Pouta, A.* ; Prins, B.P.* ; Prokopenko, I.* ; Puls, R.* ; Ruokonen, A.* ; Savolainen, M.J.* ; Schlessinger, D.* ; Schouten, J.N.* ; Seedorf, U.* ; Sen-Chowdhry, S.* ; Siminovitch, K.A.* ; Smit, J.H.* ; Spector, T.D.* ; Tan, W.* ; Teslovich, T.M.* ; Tukiainen, T.* ; Uitterlinden, A.G.* ; van der Klauw, M.M.* ; Vasan, R.S.* ; Wallace, C.* ; Wallaschofski, H.* ; Wichmann, H.-E. ; Willemsen, G.* ; Würtz, P.* ; Xu, C.* ; Yerges-Armstrong, L.M.* ; Alcohol Genome-wide Association (AlcGen) Consortium (*) ; DIAGRAM Consortium (Gieger, C. ; Huth, C. ; Grallert, H. ; Klopp, N. ; Petersen, A.-K. ; Thorand, B. ; Illig, T. ; Wichmann, H.-E. ; Meitinger, T.) ; GIANT Consortium (Peters, A. ; Thiering, E. ; Heid, I.M. ; Gieger, C. ; Grallert, H. ; Illig, T. ; Wichmann, H.-E. ; Heinrich, J.) ; Global Lipids Genetics Consortium (*) ; GOLD Consortium (*) ; ICBP Consortium (*) ; MAGIC Investigators (Grallert, H. ; Gieger, C. ; Meisinger, C. ; Thorand, B. ; Wichmann, H.-E. ; Illig, T.) ; Abecasis, G.R.* ; Ahmadi, K.R.* ; Boomsma, D.I.* ; Caulfield, M.* ; Cookson, W.O.* ; van Duijn, C.M.* ; Froguel, P.* ; Matsuda, K.* ; McCarthy, M.I.* ; Meisinger, C.* ; Mooser, V.* ; Pietiläinen, K.H.* ; Schumann, G.* ; Snieder, H.* ; Sternberg, M.J.* ; Stolk, R.P.* ; Thomas, H.C.* ; Thorsteinsdottir, U.* ; Uda, M.* ; Waeber, G.* ; Wareham, N.J.* ; Waterworth, D.M.* ; Watkins, H.* ; Whitfield, J.B.* ; Witteman, J.C.* ; Wolffenbuttel, B.H.* ; Fox, C.S.* ; Ala-Korpela, M.* ; Stefansson, K.* ; Vollenweider, P.* ; Völzke, H.* ; Schadt, E.E.* ; Scott, J.* ; Jarvelin, M.R.* ; Elliott, P.* ; Kooner, J.S.*

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

Nat. Genet. 43, 1131-1138 (2011)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Coronary-heart-disease; C-reactive protein; Salt export pump; Metabolic syndrome; Risk-factor; Hepatocellular-carcinoma; Hereditary cholestasis; Susceptibility loci; Genetic-variants; Common variants
ISSN (print) / ISBN 1061-4036
e-ISSN 1546-1718
Journal Nature Genetics
Quellenangaben Volume: 43, Issue: 11, Pages: 1131-1138 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place New York, NY
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Genetic Epidemiology (IGE)
Institute of Epidemiology (EPI)
Research Unit Molecular Epidemiology (AME)
Institute of Epidemiology II (EPI2)
Institute of Human Genetics (IHG)