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Title: Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma
Authors: 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
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
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
Keywords: Biochemistry, Genetics and Molecular Biology
Issue Date: 1-Nov-2011
Citation: Nature Genetics. Vol.43, No.11 (2011), 1131-1138
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.
ISSN: 15461718
Appears in Collections:Scopus 2011-2015

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