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

Publication ,  Journal Article
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; Das, D ...
Published in: Nat Genet
October 16, 2011

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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Published In

Nat Genet

DOI

EISSN

1546-1718

Publication Date

October 16, 2011

Volume

43

Issue

11

Start / End Page

1131 / 1138

Location

United States

Related Subject Headings

  • Polymorphism, Single Nucleotide
  • Liver
  • Humans
  • Genome-Wide Association Study
  • Enzymes
  • Developmental Biology
  • Delta-5 Fatty Acid Desaturase
  • 3105 Genetics
  • 3102 Bioinformatics and computational biology
  • 3001 Agricultural biotechnology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Chambers, J. C., Zhang, W., Sehmi, J., Li, X., Wass, M. N., Van der Harst, P., … Kooner, J. S. (2011). Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma. Nat Genet, 43(11), 1131–1138. https://doi.org/10.1038/ng.970
Chambers, John C., Weihua Zhang, Joban Sehmi, Xinzhong Li, Mark N. Wass, Pim Van der Harst, Hilma Holm, et al. “Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma.Nat Genet 43, no. 11 (October 16, 2011): 1131–38. https://doi.org/10.1038/ng.970.
Chambers JC, Zhang W, Sehmi J, Li X, Wass MN, Van der Harst P, et al. Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma. Nat Genet. 2011 Oct 16;43(11):1131–8.
Chambers, John C., et al. “Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma.Nat Genet, vol. 43, no. 11, Oct. 2011, pp. 1131–38. Pubmed, doi:10.1038/ng.970.
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. Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma. Nat Genet. 2011 Oct 16;43(11):1131–1138.

Published In

Nat Genet

DOI

EISSN

1546-1718

Publication Date

October 16, 2011

Volume

43

Issue

11

Start / End Page

1131 / 1138

Location

United States

Related Subject Headings

  • Polymorphism, Single Nucleotide
  • Liver
  • Humans
  • Genome-Wide Association Study
  • Enzymes
  • Developmental Biology
  • Delta-5 Fatty Acid Desaturase
  • 3105 Genetics
  • 3102 Bioinformatics and computational biology
  • 3001 Agricultural biotechnology