John C. ChambersWeihua ZhangJoban SehmiXinzhong LiMark N. WassPim Van Der HarstHilma HolmSerena SannaMaryam KavousiSebastian E. BaumeisterLachlan J. CoinGuohong DengChristian GiegerNancy L. Heard-CostaJouke Jan HottengaBrigitte KühnelVinod KumarVasiliki LagouLiming LiangJian'An LuanPedro Marques VidalIrene Mateo LeachPaul F. O'ReillyJohn F. PedenNilufer RahmiogluPasi SoininenElizabeth K. SpeliotesXin YuanGudmar ThorleifssonBehrooz Z. AlizadehLarry D. AtwoodIngrid B. BoreckiMorris J. BrownPimphen CharoenFrancesco CuccaDebashish DasEco J.C. De GeusAnna L. DixonAngela DöringGeorg EhretGudmundur I. EyjolfssonMartin FarrallNita G. ForouhiNele FriedrichWolfram GoesslingDaniel F. GudbjartssonTamara B. HarrisAnna Liisa HartikainenSimon HeathGideon M. HirschfieldAlbert HofmanGeorg HomuthElina HyppönenHarry L.A. JanssenToby JohnsonAntti J. KangasIdo P. KemaJens P. KühnSandra LaiMark LathropMarkus M. LerchYun LiT. Jake LiangJing Ping LinRuth J.F. LoosNicholas G. MartinMiriam F. MoffattGrant W. MontgomeryPatricia B. MunroeKiran MusunuruYusuke NakamuraChristopher J. O'DonnellIsleifur OlafssonBrenda W. PenninxImperial College LondonNational Health ServiceLondon North West Healthcare NHS TrustHammersmith HospitalRoyal Brompton HospitalUniversity of Groningen, University Medical Center GroningendeCODE geneticsConsiglio Nazionale delle RicercheErasmus University Medical CenterNetherlands Genomics InitiativeErnst-Moritz-Arndt-Universitat GreifswaldThird Military Medical UniversityHelmholtz Center Munich German Research Center for Environmental HealthBoston University School of MedicineVrije Universiteit AmsterdamInstitute of Medical Science The University of TokyoUniversity of OxfordHarvard School of Public HealthAddenbrooke's HospitalInstitut Universitaire de Medecine Sociale et Preventive LausanneWellcome Trust Centre for Human GeneticsOulun YliopistoIta-Suomen yliopistoUniversity of Michigan Medical SchoolUniversity Michigan Ann ArborGlaxoSmithKlineWashington University in St. Louis, School of MedicineCambridge Institute for Medical ResearchMahidol UniversityNational Heart and Lung InstituteThe Johns Hopkins School of MedicineCentre Hospitalier Universitaire VaudoisHopitaux universitaires de GeneveLaboratory in MjoddJohn Radcliffe HospitalBrigham and Women's HospitalHarvard Medical SchoolHarvard Stem Cell InstituteNational Institute on AgingCentre National de GenotypageUniversity of TorontoToronto Western Hospital University of TorontoUniversity of BirminghamUCL Institute of Child HealthBarts and The London Queen Mary's School of Medicine and DentistryFondation Jean Dausset - CEPHUniversity Medicine GreifswaldThe University of North Carolina at Chapel HillNational Institute of Diabetes and Digestive and Kidney DiseasesNational Heart, Lung, and Blood InstituteQueensland Institute of Medical ResearchMassachusetts General HospitalFramingham Heart StudyLandspitali University HospitalInstitute for Research in Extramural Medicine - EMGOLeiden University Medical Center - LUMCNational Institute for Health and WelfareWestfalische Wilhelms-Universitat MunsterThe Lunenfeld-Tanenbaum Research Institute of University of TorontoToronto General Research Institute University of TorontoKing's College LondonUniversity of Michigan School of Public HealthLudwig-Maximilians-Universitat MunchenKlinikum der Universitat MunchenLunenfeld-Tanenbaum Research InstituteMount Sinai HospitalTorontoUniversity of Maryland School of MedicineCentre for Medical Systems BiologyChurchill HospitalHelsinki University HospitalInstitute for Molecular Medicine FIMMHelsingin YliopistoUniversity of IcelandIcahn School of Medicine at Mount SinaiHealth Protection Agency2018-05-032018-05-032011-11-01Nature Genetics. Vol.43, No.11 (2011), 1131-113815461718106140362-s2.0-80055024880https://repository.li.mahidol.ac.th/handle/20.500.14594/11450Concentrations 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.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyArticleSCOPUS10.1038/ng.970