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

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), Collaborators

Research output: Contribution to journalArticle

274 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1131-1138
Number of pages8
JournalNature Genetics
Volume43 43
Issue number11 11
DOIs
StatePublished - Nov 1 2011
Externally publishedYes

Fingerprint

Genome-Wide Association Study
Liver
Enzymes
Genes
Glycomics
Metabolomics
Membrane Glycoproteins
Carbohydrate Metabolism
Gene Expression Profiling
Lipid Metabolism
Glutathione
Liver Diseases
Immunity
Inflammation
Glucose

ASJC Scopus subject areas

  • Genetics

Cite this

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), & Collaborators (2011). Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma. Nature Genetics, 43 43(11 11), 1131-1138. https://doi.org/10.1038/ng.970

Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma. / 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); Collaborators.

In: Nature Genetics, Vol. 43 43, No. 11 11, 01.11.2011, p. 1131-1138.

Research output: Contribution to journalArticle

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) & Collaborators 2011, 'Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma', Nature Genetics, vol. 43 43, no. 11 11, pp. 1131-1138. https://doi.org/10.1038/ng.970
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), Collaborators. Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma. Nature Genetics. 2011 Nov 1;43 43(11 11):1131-1138. https://doi.org/10.1038/ng.970
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) ; Collaborators. / Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma. In: Nature Genetics. 2011 ; Vol. 43 43, No. 11 11. pp. 1131-1138.
@article{c368a130afe64316b0c8dc62da1c68c7,
title = "Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma",
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.",
author = "{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)} and Collaborators and Chambers, {J. C.} and W. Zhang and J. Sehmi and X. Li and Wass, {M. N.} and {Van der Harst}, P. and H. Holm and S. Sanna and M. Kavousi and Baumeister, {S. E.} and Coin, {L. J.} and G. Deng and C. Gieger and Heard-Costa, {N. L.} and Hottenga, {J. J.} and B. K{\"u}hnel and V. Kumar and V. Lagou and L. Liang and J. Luan and Vidal, {P. M.} and {Mateo Leach}, I. and O'reilly, {P. F.} and Peden, {J. F.} and N. Rahmioglu and P. Soininen and Speliotes, {E. K.} and X. Yuan and G. Thorleifsson and Alizadeh, {B. Z.} and Atwood, {L. D.} and Borecki, {I. B.} and Brown, {M. J.} and P. Charoen and F. Cucca and D. Das and {de Geus}, {E. J.} and Dixon, {A. L.} and A. D{\"o}ring and G. Ehret and Eyjolfsson, {G. I.} and M. Farrall and Forouhi, {N. G.} and N. Friedrich and W. Goessling and Gudbjartsson, {D. F.} and Harris, {T. B.} and Hartikainen, {A. L.} and S. Heath and Kaplan, {Robert C.}",
year = "2011",
month = "11",
day = "1",
doi = "10.1038/ng.970",
language = "English (US)",
volume = "43 43",
pages = "1131--1138",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "11 11",

}

TY - JOUR

T1 - Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma

AU - 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) C

AU - Collaborators

AU - Chambers, J. C.

AU - Zhang, W.

AU - Sehmi, J.

AU - Li, X.

AU - Wass, M. N.

AU - Van der Harst, P.

AU - Holm, H.

AU - Sanna, S.

AU - Kavousi, M.

AU - Baumeister, S. E.

AU - Coin, L. J.

AU - Deng, G.

AU - Gieger, C.

AU - Heard-Costa, N. L.

AU - Hottenga, J. J.

AU - Kühnel, B.

AU - Kumar, V.

AU - Lagou, V.

AU - Liang, L.

AU - Luan, J.

AU - Vidal, P. M.

AU - Mateo Leach, I.

AU - O'reilly, P. F.

AU - Peden, J. F.

AU - Rahmioglu, N.

AU - Soininen, P.

AU - Speliotes, E. K.

AU - Yuan, X.

AU - Thorleifsson, G.

AU - Alizadeh, B. Z.

AU - Atwood, L. D.

AU - Borecki, I. B.

AU - Brown, M. J.

AU - Charoen, P.

AU - Cucca, F.

AU - Das, D.

AU - de Geus, E. J.

AU - Dixon, A. L.

AU - Döring, A.

AU - Ehret, G.

AU - Eyjolfsson, G. I.

AU - Farrall, M.

AU - Forouhi, N. G.

AU - Friedrich, N.

AU - Goessling, W.

AU - Gudbjartsson, D. F.

AU - Harris, T. B.

AU - Hartikainen, A. L.

AU - Heath, S.

AU - Kaplan, Robert C.

PY - 2011/11/1

Y1 - 2011/11/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=80055024880&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80055024880&partnerID=8YFLogxK

U2 - 10.1038/ng.970

DO - 10.1038/ng.970

M3 - Article

VL - 43 43

SP - 1131

EP - 1138

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 11 11

ER -