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

AUTHOR GROUP; N.G. Martin; G.W. Montgomery; B.W.J.H. Penninx; I. Prokopenko; T.D. Spector; A.G. Uitterlinden; G. Willemsen; G.R. Abecasis; D.I. Boomsma; C.M. van Duijn; H. Snieder; J.B. Whitfield; J.C.M. Witteman; C.S. Fox; M. Ala-Korpela; K. Stefansson; P. Vollenweider; H. Völzke; E.E. Schadt; J. Scott; M.R. Jarvelin; P. Elliot; J.S. Kooner

doi:https://doi.org/10.1038/ng.970

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

AUTHOR GROUP, N.G. Martin, G.W. Montgomery, B.W.J.H. Penninx, I. Prokopenko, T.D. Spector, A.G. Uitterlinden, G. Willemsen, G.R. Abecasis, D.I. Boomsma, C.M. van Duijn, H. Snieder, J.B. Whitfield, J.C.M. Witteman, C.S. Fox, M. Ala-Korpela, K. Stefansson, P. Vollenweider, H. Völzke, E.E. SchadtJ. Scott, M.R. Jarvelin, P. Elliot, J.S. Kooner

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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 language	English
Pages (from-to)	1131-U129
Journal	Nature Genetics
Volume	43
Issue number	11
DOIs	https://doi.org/10.1038/ng.970
Publication status	Published - 2011

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Cite this

AUTHOR GROUP, Martin, N. G., Montgomery, G. W., Penninx, B. W. J. H., Prokopenko, I., Spector, T. D., Uitterlinden, A. G., Willemsen, G., Abecasis, G. R., Boomsma, D. I., van Duijn, C. M., Snieder, H., Whitfield, J. B., Witteman, J. C. M., Fox, C. S., Ala-Korpela, M., Stefansson, K., Vollenweider, P., Völzke, H., ... Kooner, J. S. (2011). Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma. Nature Genetics, 43(11), 1131-U129. https://doi.org/10.1038/ng.970

@article{dfc6fca899b14e009da6ed16418aa9b0,

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 = "Chambers, {John C.} and Weihua Zhang and Joban Sehmi and Xinzhong Li and Wass, {Mark N.} and {van der Harst}, Pim and Hilma Holm and Serena Sanna and Maryam Kavousi and Baumeister, {Sebastian E.} and Coin, {Lachlan J.} and Guohong Deng and Christian Gieger and Heard-Costa, {Nancy L.} and Jouke-Jan Hottenga and Brigitte K{\"u}hnel and Vinod Kumar and Vasiliki Lagou and Liming Liang and Jian'an Luan and Vidal, {Pedro Marques} and {Mateo Leach}, Irene and O'Reilly, {Paul F.} and Peden, {John F.} and Nilufer Rahmioglu and Pasi Soininen and Speliotes, {Elizabeth K.} and Xin Yuan and Gudmar Thorleifsson and Alizadeh, {Behrooz Z.} and Atwood, {Larry D.} and Borecki, {Ingrid B.} and Brown, {Morris J.} and Pimphen Charoen and Francesco Cucca and Debashish Das and {de Geus}, {Eco J. C.} and Dixon, {Anna L.} and Angela D{\"o}ring and Georg Ehret and Eyjolfsson, {Gudmundur I.} and Martin Farrall and Forouhi, {Nita G.} and Nele Friedrich and {AUTHOR GROUP} and J. Yang and Fouchier, {S. W.} and Hovingh, {G. Kees} and Boekholdt, {S. M.} and Kastelein, {J. J.} and P. Henneman and N.G. Martin and G.W. Montgomery and B.W.J.H. Penninx and I. Prokopenko and T.D. Spector and A.G. Uitterlinden and G. Willemsen and G.R. Abecasis and D.I. Boomsma and {van Duijn}, C.M. and H. Snieder and J.B. Whitfield and J.C.M. Witteman and C.S. Fox and M. Ala-Korpela and K. Stefansson and P. Vollenweider and H. V{\"o}lzke and E.E. Schadt and J. Scott and M.R. Jarvelin and P. Elliot and J.S. Kooner",

year = "2011",

doi = "https://doi.org/10.1038/ng.970",

language = "English",

volume = "43",

pages = "1131--U129",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "11",

}

AUTHOR GROUP, Martin, NG, Montgomery, GW, Penninx, BWJH, Prokopenko, I, Spector, TD, Uitterlinden, AG, Willemsen, G, Abecasis, GR, Boomsma, DI, van Duijn, CM, Snieder, H, Whitfield, JB, Witteman, JCM, Fox, CS, Ala-Korpela, M, Stefansson, K, Vollenweider, P, Völzke, H, Schadt, EE, Scott, J, Jarvelin, MR, Elliot, P & Kooner, JS 2011, 'Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma', Nature Genetics, vol. 43, no. 11, pp. 1131-U129. https://doi.org/10.1038/ng.970

TY - JOUR

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

AU - Chambers, John C.

AU - Zhang, Weihua

AU - Sehmi, Joban

AU - Li, Xinzhong

AU - Wass, Mark N.

AU - van der Harst, Pim

AU - Holm, Hilma

AU - Sanna, Serena

AU - Kavousi, Maryam

AU - Baumeister, Sebastian E.

AU - Coin, Lachlan J.

AU - Deng, Guohong

AU - Gieger, Christian

AU - Heard-Costa, Nancy L.

AU - Hottenga, Jouke-Jan

AU - Kühnel, Brigitte

AU - Kumar, Vinod

AU - Lagou, Vasiliki

AU - Liang, Liming

AU - Luan, Jian'an

AU - Vidal, Pedro Marques

AU - Mateo Leach, Irene

AU - O'Reilly, Paul F.

AU - Peden, John F.

AU - Rahmioglu, Nilufer

AU - Soininen, Pasi

AU - Speliotes, Elizabeth K.

AU - Yuan, Xin

AU - Thorleifsson, Gudmar

AU - Alizadeh, Behrooz Z.

AU - Atwood, Larry D.

AU - Borecki, Ingrid B.

AU - Brown, Morris J.

AU - Charoen, Pimphen

AU - Cucca, Francesco

AU - Das, Debashish

AU - de Geus, Eco J. C.

AU - Dixon, Anna L.

AU - Döring, Angela

AU - Ehret, Georg

AU - Eyjolfsson, Gudmundur I.

AU - Farrall, Martin

AU - Forouhi, Nita G.

AU - Friedrich, Nele

AU - AUTHOR GROUP

AU - Yang, J.

AU - Fouchier, S. W.

AU - Hovingh, G. Kees

AU - Boekholdt, S. M.

AU - Kastelein, J. J.

AU - Henneman, P.

AU - Martin, N.G.

AU - Montgomery, G.W.

AU - Penninx, B.W.J.H.

AU - Prokopenko, I.

AU - Spector, T.D.

AU - Uitterlinden, A.G.

AU - Willemsen, G.

AU - Abecasis, G.R.

AU - Boomsma, D.I.

AU - van Duijn, C.M.

AU - Snieder, H.

AU - Whitfield, J.B.

AU - Witteman, J.C.M.

AU - Fox, C.S.

AU - Ala-Korpela, M.

AU - Stefansson, K.

AU - Vollenweider, P.

AU - Völzke, H.

AU - Schadt, E.E.

AU - Scott, J.

AU - Jarvelin, M.R.

AU - Elliot, P.

AU - Kooner, J.S.

PY - 2011

Y1 - 2011

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

U2 - https://doi.org/10.1038/ng.970

DO - https://doi.org/10.1038/ng.970

M3 - Article

C2 - 22001757

SN - 1061-4036

VL - 43

SP - 1131-U129

JO - Nature Genetics

JF - Nature Genetics

IS - 11

ER -