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

Issued Date

2011-11-01

Resource Type

Article

ISSN

15461718
10614036

DOI

10.1038/ng.970

Other identifier(s)

2-s2.0-80055024880

Rights

Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

Nature Genetics. Vol.43, No.11 (2011), 1131-1138

Suggested Citation

John C. Chambers, Weihua Zhang, Joban Sehmi, Xinzhong Li, Mark N. Wass, Pim Van Der Harst, Hilma Holm, Serena Sanna, Maryam Kavousi, Sebastian E. Baumeister, Lachlan J. Coin, Guohong Deng, Christian Gieger, Nancy L. Heard-Costa, Jouke Jan Hottenga, Brigitte Kühnel, Vinod Kumar, Vasiliki Lagou, Liming Liang, Jian'An Luan, Pedro Marques Vidal, Irene Mateo Leach, Paul F. O'Reilly, John F. Peden, Nilufer Rahmioglu, Pasi Soininen, Elizabeth K. Speliotes, Xin Yuan, Gudmar Thorleifsson, Behrooz Z. Alizadeh, Larry D. Atwood, Ingrid B. Borecki, Morris J. Brown, Pimphen Charoen, Francesco Cucca, Debashish Das, Eco J.C. De Geus, Anna L. Dixon, Angela Döring, Georg Ehret, Gudmundur I. Eyjolfsson, Martin Farrall, Nita G. Forouhi, Nele Friedrich, Wolfram Goessling, Daniel F. Gudbjartsson, Tamara B. Harris, Anna Liisa Hartikainen, Simon Heath, Gideon M. Hirschfield, Albert Hofman, Georg Homuth, Elina Hyppönen, Harry L.A. Janssen, Toby Johnson, Antti J. Kangas, Ido P. Kema, Jens P. Kühn, Sandra Lai, Mark Lathrop, Markus M. Lerch, Yun Li, T. Jake Liang, Jing Ping Lin, Ruth J.F. Loos, Nicholas G. Martin, Miriam F. Moffatt, Grant W. Montgomery, Patricia B. Munroe, Kiran Musunuru, Yusuke Nakamura, Christopher J. O'Donnell, Isleifur Olafsson, Brenda W. Penninx Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma. Nature Genetics. Vol.43, No.11 (2011), 1131-1138. doi:10.1038/ng.970 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/11450

Research Projects

Organizational Units

Authors

Journal Issue

Thesis

Title

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

Author(s)

John C. Chambers
 Weihua Zhang
 Joban Sehmi
 Xinzhong Li
 Mark N. Wass
 Pim Van Der Harst
 Hilma Holm
 Serena Sanna
 Maryam Kavousi
 Sebastian E. Baumeister
 Lachlan J. Coin
 Guohong Deng
 Christian Gieger
 Nancy L. Heard-Costa
 Jouke Jan Hottenga
 Brigitte Kühnel
 Vinod Kumar
 Vasiliki Lagou
 Liming Liang
 Jian'An Luan
 Pedro Marques Vidal
 Irene Mateo Leach
 Paul F. O'Reilly
 John F. Peden
 Nilufer Rahmioglu
 Pasi Soininen
 Elizabeth K. Speliotes
 Xin Yuan
 Gudmar Thorleifsson
 Behrooz Z. Alizadeh
 Larry D. Atwood
 Ingrid B. Borecki
 Morris J. Brown
 Pimphen Charoen
 Francesco Cucca
 Debashish Das
 Eco J.C. De Geus
 Anna L. Dixon
 Angela Döring
 Georg Ehret
 Gudmundur I. Eyjolfsson
 Martin Farrall
 Nita G. Forouhi
 Nele Friedrich
 Wolfram Goessling
 Daniel F. Gudbjartsson
 Tamara B. Harris
 Anna Liisa Hartikainen
 Simon Heath
 Gideon M. Hirschfield
 Albert Hofman
 Georg Homuth
 Elina Hyppönen
 Harry L.A. Janssen
 Toby Johnson
 Antti J. Kangas
 Ido P. Kema
 Jens P. Kühn
 Sandra Lai
 Mark Lathrop
 Markus M. Lerch
 Yun Li
 T. Jake Liang
 Jing Ping Lin
 Ruth J.F. Loos
 Nicholas G. Martin
 Miriam F. Moffatt
 Grant W. Montgomery
 Patricia B. Munroe
 Kiran Musunuru
 Yusuke Nakamura
 Christopher J. O'Donnell
 Isleifur Olafsson
 Brenda W. Penninx

Other Contributor(s)

Imperial College London
 National Health Service
 London North West Healthcare NHS Trust
 Hammersmith Hospital
 Royal Brompton Hospital
 University of Groningen, University Medical Center Groningen
 deCODE genetics
 Consiglio Nazionale delle Ricerche
 Erasmus University Medical Center
 Netherlands Genomics Initiative
 Ernst-Moritz-Arndt-Universitat Greifswald
 Third Military Medical University
 Helmholtz Center Munich German Research Center for Environmental Health
 Boston University School of Medicine
 Vrije Universiteit Amsterdam
 Institute of Medical Science The University of Tokyo
 University of Oxford
 Harvard School of Public Health
 Addenbrooke's Hospital
 Institut Universitaire de Medecine Sociale et Preventive Lausanne
 Wellcome Trust Centre for Human Genetics
 Oulun Yliopisto
 Ita-Suomen yliopisto
 University of Michigan Medical School
 University Michigan Ann Arbor
 GlaxoSmithKline
 Washington University in St. Louis, School of Medicine
 Cambridge Institute for Medical Research
 Mahidol University
 National Heart and Lung Institute
 The Johns Hopkins School of Medicine
 Centre Hospitalier Universitaire Vaudois
 Hopitaux universitaires de Geneve
 Laboratory in Mjodd
 John Radcliffe Hospital
 Brigham and Women's Hospital
 Harvard Medical School
 Harvard Stem Cell Institute
 National Institute on Aging
 Centre National de Genotypage
 University of Toronto
 Toronto Western Hospital University of Toronto
 University of Birmingham
 UCL Institute of Child Health
 Barts and The London Queen Mary's School of Medicine and Dentistry
 Fondation Jean Dausset - CEPH
 University Medicine Greifswald
 The University of North Carolina at Chapel Hill
 National Institute of Diabetes and Digestive and Kidney Diseases
 National Heart, Lung, and Blood Institute
 Queensland Institute of Medical Research
 Massachusetts General Hospital
 Framingham Heart Study
 Landspitali University Hospital
 Institute for Research in Extramural Medicine - EMGO
 Leiden University Medical Center - LUMC
 National Institute for Health and Welfare
 Westfalische Wilhelms-Universitat Munster
 The Lunenfeld-Tanenbaum Research Institute of University of Toronto
 Toronto General Research Institute University of Toronto
 King's College London
 University of Michigan School of Public Health
 Ludwig-Maximilians-Universitat Munchen
 Klinikum der Universitat Munchen
 Lunenfeld-Tanenbaum Research InstituteMount Sinai HospitalToronto
 University of Maryland School of Medicine
 Centre for Medical Systems Biology
 Churchill Hospital
 Helsinki University Hospital
 Institute for Molecular Medicine FIMM
 Helsingin Yliopisto
 University of Iceland
 Icahn School of Medicine at Mount Sinai
 Health Protection Agency

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. © 2011 Nature America, Inc. All rights reserved.

Keyword(s)

Biochemistry, Genetics and Molecular Biology

Availability

URI

https://repository.li.mahidol.ac.th/handle/20.500.14594/11450

Collections

Scopus 2011-2015