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

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 )....

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Main 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
Other Authors: Imperial College London
Format: Article
Published: 2018
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Online Access:https://repository.li.mahidol.ac.th/handle/123456789/11450
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id th-mahidol.11450
record_format dspace
institution Mahidol University
building Mahidol University Library
continent Asia
country Thailand
Thailand
content_provider Mahidol University Library
collection Mahidol University Institutional Repository
topic Biochemistry, Genetics and Molecular Biology
spellingShingle Biochemistry, Genetics and Molecular Biology
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
description 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.
author2 Imperial College London
author_facet Imperial College London
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
format Article
author 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
author_sort John C. Chambers
title Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma
title_short Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma
title_full Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma
title_fullStr Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma
title_full_unstemmed Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma
title_sort genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma
publishDate 2018
url https://repository.li.mahidol.ac.th/handle/123456789/11450
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spelling th-mahidol.114502018-05-03T14:59:46Z Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma 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 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 Biochemistry, Genetics and Molecular Biology 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. 2018-05-03T07:59:46Z 2018-05-03T07:59:46Z 2011-11-01 Article Nature Genetics. Vol.43, No.11 (2011), 1131-1138 10.1038/ng.970 15461718 10614036 2-s2.0-80055024880 https://repository.li.mahidol.ac.th/handle/123456789/11450 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=80055024880&origin=inward