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

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, JJ, 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, EJ, Dixon, AL, Döring, A, Ehret, G, Eyjolfsson, GI, Farrall, M, Forouhi, NG, Friedrich, N, Goessling, W, Gudbjartsson, DF, Harris, TB, Hartikainen, AL, Heath, S, Hirschfield, GM, Hofman, A, Homuth, G, Hyppönen, E, Janssen, HL, Johnson, T, Kangas, AJ, Kema, IP, Kühn, JP, Lai, S, Lathrop, M, Lerch, MM, Li, Y, Liang, TJ, Lin, JP, Loos, RJ, 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, JN, 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, HE, 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) Consortiu, , 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 (, , 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, MJ, Stolk, RP, Thomas, HC, Thorsteinsdottir, U, Uda, M, Waeber, G, Wareham, NJ, Waterworth, DM, Watkins, H, Whitfield, JB, Witteman, JC, Wolffenbuttel, BH, Fox, CS, Ala-Korpela, M, Stefansson, K, Vollenweider, P, Völzke, H, Schadt, EE, Scott, J, Järvelin, MR, Elliott, P and Kooner, JS (2011) Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma. Nat Genet, 43 (11). pp. 1131-1138.

Full text not available from this repository.

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.

Item Type: Article
Authors :
NameEmailORCID
Chambers, JCUNSPECIFIEDUNSPECIFIED
Zhang, WUNSPECIFIEDUNSPECIFIED
Sehmi, JUNSPECIFIEDUNSPECIFIED
Li, XUNSPECIFIEDUNSPECIFIED
Wass, MNUNSPECIFIEDUNSPECIFIED
Van der Harst, PUNSPECIFIEDUNSPECIFIED
Holm, HUNSPECIFIEDUNSPECIFIED
Sanna, SUNSPECIFIEDUNSPECIFIED
Kavousi, MUNSPECIFIEDUNSPECIFIED
Baumeister, SEUNSPECIFIEDUNSPECIFIED
Coin, LJUNSPECIFIEDUNSPECIFIED
Deng, GUNSPECIFIEDUNSPECIFIED
Gieger, CUNSPECIFIEDUNSPECIFIED
Heard-Costa, NLUNSPECIFIEDUNSPECIFIED
Hottenga, JJUNSPECIFIEDUNSPECIFIED
Kühnel, BUNSPECIFIEDUNSPECIFIED
Kumar, VUNSPECIFIEDUNSPECIFIED
Lagou, VUNSPECIFIEDUNSPECIFIED
Liang, LUNSPECIFIEDUNSPECIFIED
Luan, JUNSPECIFIEDUNSPECIFIED
Vidal, PMUNSPECIFIEDUNSPECIFIED
Mateo Leach, IUNSPECIFIEDUNSPECIFIED
O'Reilly, PFUNSPECIFIEDUNSPECIFIED
Peden, JFUNSPECIFIEDUNSPECIFIED
Rahmioglu, NUNSPECIFIEDUNSPECIFIED
Soininen, PUNSPECIFIEDUNSPECIFIED
Speliotes, EKUNSPECIFIEDUNSPECIFIED
Yuan, XUNSPECIFIEDUNSPECIFIED
Thorleifsson, GUNSPECIFIEDUNSPECIFIED
Alizadeh, BZUNSPECIFIEDUNSPECIFIED
Atwood, LDUNSPECIFIEDUNSPECIFIED
Borecki, IBUNSPECIFIEDUNSPECIFIED
Brown, MJUNSPECIFIEDUNSPECIFIED
Charoen, PUNSPECIFIEDUNSPECIFIED
Cucca, FUNSPECIFIEDUNSPECIFIED
Das, DUNSPECIFIEDUNSPECIFIED
de Geus, EJUNSPECIFIEDUNSPECIFIED
Dixon, ALUNSPECIFIEDUNSPECIFIED
Döring, AUNSPECIFIEDUNSPECIFIED
Ehret, GUNSPECIFIEDUNSPECIFIED
Eyjolfsson, GIUNSPECIFIEDUNSPECIFIED
Farrall, MUNSPECIFIEDUNSPECIFIED
Forouhi, NGUNSPECIFIEDUNSPECIFIED
Friedrich, NUNSPECIFIEDUNSPECIFIED
Goessling, WUNSPECIFIEDUNSPECIFIED
Gudbjartsson, DFUNSPECIFIEDUNSPECIFIED
Harris, TBUNSPECIFIEDUNSPECIFIED
Hartikainen, ALUNSPECIFIEDUNSPECIFIED
Heath, SUNSPECIFIEDUNSPECIFIED
Hirschfield, GMUNSPECIFIEDUNSPECIFIED
Hofman, AUNSPECIFIEDUNSPECIFIED
Homuth, GUNSPECIFIEDUNSPECIFIED
Hyppönen, EUNSPECIFIEDUNSPECIFIED
Janssen, HLUNSPECIFIEDUNSPECIFIED
Johnson, TUNSPECIFIEDUNSPECIFIED
Kangas, AJUNSPECIFIEDUNSPECIFIED
Kema, IPUNSPECIFIEDUNSPECIFIED
Kühn, JPUNSPECIFIEDUNSPECIFIED
Lai, SUNSPECIFIEDUNSPECIFIED
Lathrop, MUNSPECIFIEDUNSPECIFIED
Lerch, MMUNSPECIFIEDUNSPECIFIED
Li, YUNSPECIFIEDUNSPECIFIED
Liang, TJUNSPECIFIEDUNSPECIFIED
Lin, JPUNSPECIFIEDUNSPECIFIED
Loos, RJUNSPECIFIEDUNSPECIFIED
Martin, NGUNSPECIFIEDUNSPECIFIED
Moffatt, MFUNSPECIFIEDUNSPECIFIED
Montgomery, GWUNSPECIFIEDUNSPECIFIED
Munroe, PBUNSPECIFIEDUNSPECIFIED
Musunuru, KUNSPECIFIEDUNSPECIFIED
Nakamura, YUNSPECIFIEDUNSPECIFIED
O'Donnell, CJUNSPECIFIEDUNSPECIFIED
Olafsson, IUNSPECIFIEDUNSPECIFIED
Penninx, BWUNSPECIFIEDUNSPECIFIED
Pouta, AUNSPECIFIEDUNSPECIFIED
Prins, BPUNSPECIFIEDUNSPECIFIED
Prokopenko, IUNSPECIFIEDUNSPECIFIED
Puls, RUNSPECIFIEDUNSPECIFIED
Ruokonen, AUNSPECIFIEDUNSPECIFIED
Savolainen, MJUNSPECIFIEDUNSPECIFIED
Schlessinger, DUNSPECIFIEDUNSPECIFIED
Schouten, JNUNSPECIFIEDUNSPECIFIED
Seedorf, UUNSPECIFIEDUNSPECIFIED
Sen-Chowdhry, SUNSPECIFIEDUNSPECIFIED
Siminovitch, KAUNSPECIFIEDUNSPECIFIED
Smit, JHUNSPECIFIEDUNSPECIFIED
Spector, TDUNSPECIFIEDUNSPECIFIED
Tan, WUNSPECIFIEDUNSPECIFIED
Teslovich, TMUNSPECIFIEDUNSPECIFIED
Tukiainen, TUNSPECIFIEDUNSPECIFIED
Uitterlinden, AGUNSPECIFIEDUNSPECIFIED
Van der Klauw, MMUNSPECIFIEDUNSPECIFIED
Vasan, RSUNSPECIFIEDUNSPECIFIED
Wallace, CUNSPECIFIEDUNSPECIFIED
Wallaschofski, HUNSPECIFIEDUNSPECIFIED
Wichmann, HEUNSPECIFIEDUNSPECIFIED
Willemsen, GUNSPECIFIEDUNSPECIFIED
Würtz, PUNSPECIFIEDUNSPECIFIED
Xu, CUNSPECIFIEDUNSPECIFIED
Yerges-Armstrong, LMUNSPECIFIEDUNSPECIFIED
Alcohol Genome-wide Association (AlcGen) Consortium, UNSPECIFIEDUNSPECIFIED
Diabetes Genetics Replication and Meta-analyses (DIAGRAM+) Study, UNSPECIFIEDUNSPECIFIED
Genetic Investigation of Anthropometric Traits (GIANT) Consortiu, UNSPECIFIEDUNSPECIFIED
Global Lipids Genetics Consortium, UNSPECIFIEDUNSPECIFIED
Genetics of Liver Disease (GOLD) Consortium, UNSPECIFIEDUNSPECIFIED
International Consortium for Blood Pressure (ICBP-GWAS), UNSPECIFIEDUNSPECIFIED
Meta-analyses of Glucose and Insulin-Related Traits Consortium (, UNSPECIFIEDUNSPECIFIED
Abecasis, GRUNSPECIFIEDUNSPECIFIED
Ahmadi, KRk.ahmadi@surrey.ac.ukUNSPECIFIED
Boomsma, DIUNSPECIFIEDUNSPECIFIED
Caulfield, MUNSPECIFIEDUNSPECIFIED
Cookson, WOUNSPECIFIEDUNSPECIFIED
van Duijn, CMUNSPECIFIEDUNSPECIFIED
Froguel, PUNSPECIFIEDUNSPECIFIED
Matsuda, KUNSPECIFIEDUNSPECIFIED
McCarthy, MIUNSPECIFIEDUNSPECIFIED
Meisinger, CUNSPECIFIEDUNSPECIFIED
Mooser, VUNSPECIFIEDUNSPECIFIED
Pietiläinen, KHUNSPECIFIEDUNSPECIFIED
Schumann, GUNSPECIFIEDUNSPECIFIED
Snieder, HUNSPECIFIEDUNSPECIFIED
Sternberg, MJUNSPECIFIEDUNSPECIFIED
Stolk, RPUNSPECIFIEDUNSPECIFIED
Thomas, HCUNSPECIFIEDUNSPECIFIED
Thorsteinsdottir, UUNSPECIFIEDUNSPECIFIED
Uda, MUNSPECIFIEDUNSPECIFIED
Waeber, GUNSPECIFIEDUNSPECIFIED
Wareham, NJUNSPECIFIEDUNSPECIFIED
Waterworth, DMUNSPECIFIEDUNSPECIFIED
Watkins, HUNSPECIFIEDUNSPECIFIED
Whitfield, JBUNSPECIFIEDUNSPECIFIED
Witteman, JCUNSPECIFIEDUNSPECIFIED
Wolffenbuttel, BHUNSPECIFIEDUNSPECIFIED
Fox, CSUNSPECIFIEDUNSPECIFIED
Ala-Korpela, MUNSPECIFIEDUNSPECIFIED
Stefansson, KUNSPECIFIEDUNSPECIFIED
Vollenweider, PUNSPECIFIEDUNSPECIFIED
Völzke, HUNSPECIFIEDUNSPECIFIED
Schadt, EEUNSPECIFIEDUNSPECIFIED
Scott, JUNSPECIFIEDUNSPECIFIED
Järvelin, MRUNSPECIFIEDUNSPECIFIED
Elliott, PUNSPECIFIEDUNSPECIFIED
Kooner, JSUNSPECIFIEDUNSPECIFIED
Date : November 2011
Identification Number : 10.1038/ng.970
Uncontrolled Keywords : Enzymes, Genome-Wide Association Study, Humans, Liver, Polymorphism, Single Nucleotide
Depositing User : Symplectic Elements
Date Deposited : 17 May 2017 09:48
Last Modified : 17 May 2017 14:44
URI: http://epubs.surrey.ac.uk/id/eprint/825174

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