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

2.50
Hdl Handle:
http://hdl.handle.net/10146/232031
Title:
Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma.
Authors:
Chambers, John C.; Zhang, Weihua; Sehmi, Joban; Li, Xinzhong; Wass, Mark N.; Van der Harst, Pim; Holm, Hilma; Sanna, Serena; Kavousi, Maryam; Baumeister, Sebastian E.; Coin, Lachlan J.; Abecasis, Goncalo R.; Ahmadi, Kourosh R.; Boomsma, Dorret I.; Caulfield, Mark; Cookson, William O.; van Duijn, Cornelia M.; Froguel, Philippe; Matsuda, Koichi; McCarthy, Mark I.; Meisinger, Christa; Deng, Guohong; Mooser, Vincent; Pietiläinen, Kirsi H.; Schumann, Gunter; Snieder, Harold; Sternberg, Michael J. E.; Stolk, Ronald P.; Thomas, Howard C.; Thorsteinsdottir, Unnur; Uda, Manuela; Waeber, Gérard; Gieger, Christian; Wareham, Nicholas J.; Waterworth, Dawn M.; Watkins, Hugh; Whitfield, John B.; Witteman, Jacqueline C. M.; Wolffenbuttel, Bruce H. R.; Fox, Caroline S.; Ala-Korpela, Mika; Stefansson, Kari; Vollenweider, Peter; Heard-Costa, Nancy L.; Völzke, Henry; Schadt, Eric E.; Scott, James; Järvelin, Marjo-Riitta; Elliott, Paul; Kooner, Jaspal S.; Hottenga, Jouke-Jan; Kühnel, Brigitte; Kumar, Vinod; Lagou, Vasiliki; Liang, Liming; Luan, Jian'an; Vidal, Pedro Marques; Mateo Leach, Irene; O'Reilly, Paul F.; Peden, John F.; Rahmioglu, Nilufer; Soininen, Pasi; Speliotes, Elizabeth K.; Yuan, Xin; Thorleifsson, Gudmar; Alizadeh, Behrooz Z.; Atwood, Larry D.; Borecki, Ingrid B.; Brown, Morris J.; Charoen, Pimphen; Cucca, Francesco; Das, Debashish; de Geus, Eco J. C.; Dixon, Anna L.; Döring, Angela; Ehret, Georg; Eyjolfsson, Gudmundur I.; Farrall, Martin; Forouhi, Nita G.; Friedrich, Nele; Goessling, Wolfram; Gudbjartsson, Daniel F.; Harris, Tamara B.; Hartikainen, Anna-Liisa; Heath, Simon; Hirschfield, Gideon M.; Hofman, Albert; Homuth, Georg; Hyppönen, Elina; Janssen, Harry L. A.; Johnson, Toby; Kangas, Antti J.; Kema, Ido P.; Kühn, Jens P.; Lai, Sandra; Lathrop, Mark; Lerch, Markus M.; Li, Yun; Liang, T. Jake; Lin, Jing-Ping; Loos, Ruth J. F.; Martin, Nicholas G.; Moffatt, Miriam F.; Montgomery, Grant W.; Munroe, Patricia B.; Musunuru, Kiran; Nakamura, Yusuke; O'Donnell, Christopher J.; Olafsson, Isleifur; Penninx, Brenda W.; Pouta, Anneli; Prins, Bram P.; Prokopenko, Inga; Puls, Ralf; Ruokonen, Aimo; Savolainen, Markku J.; Schlessinger, David; Schouten, Jeoffrey N. L.; Seedorf, Udo; Sen-Chowdhry, Srijita; Siminovitch, Katherine A.; Smit, Johannes H.; Spector, Timothy D.; Tan, Wenting; Teslovich, Tanya M.; Tukiainen, Taru; Uitterlinden, Andre G.; Van der Klauw, Melanie M.; Vasan, Ramachandran S.; Wallace, Chris; Wallaschofski, Henri; Wichmann, H-Erich; Willemsen, Gonneke; Würtz, Peter; Xu, Chun; Yerges-Armstrong, Laura M.
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.
Citation:
Nat. Genet. 2011, 43 (11):1131-1138
Journal:
Nature Genetics
Issue Date:
Nov-2011
URI:
http://hdl.handle.net/10146/232031
DOI:
10.1038/ng.970
PubMed ID:
22001757
Additional Links:
http://www.nature.com/ng/journal/v43/n11/full/ng.970.html
Type:
Article
Language:
en
ISSN:
1546-1718
Sponsors:
Major support for the work came from European Commission (FP5, FP6 and FP7); European Science Foundation; European Science Council;
Appears in Collections:
Articles

Full metadata record

DC FieldValue Language
dc.contributor.authorChambers, John C.en_GB
dc.contributor.authorZhang, Weihuaen_GB
dc.contributor.authorSehmi, Jobanen_GB
dc.contributor.authorLi, Xinzhongen_GB
dc.contributor.authorWass, Mark N.en_GB
dc.contributor.authorVan der Harst, Pimen_GB
dc.contributor.authorHolm, Hilmaen_GB
dc.contributor.authorSanna, Serenaen_GB
dc.contributor.authorKavousi, Maryamen_GB
dc.contributor.authorBaumeister, Sebastian E.en_GB
dc.contributor.authorCoin, Lachlan J.en_GB
dc.contributor.authorAbecasis, Goncalo R.en_GB
dc.contributor.authorAhmadi, Kourosh R.en_GB
dc.contributor.authorBoomsma, Dorret I.en_GB
dc.contributor.authorCaulfield, Marken_GB
dc.contributor.authorCookson, William O.en_GB
dc.contributor.authorvan Duijn, Cornelia M.en_GB
dc.contributor.authorFroguel, Philippeen_GB
dc.contributor.authorMatsuda, Koichien_GB
dc.contributor.authorMcCarthy, Mark I.en_GB
dc.contributor.authorMeisinger, Christaen_GB
dc.contributor.authorDeng, Guohongen_GB
dc.contributor.authorMooser, Vincenten_GB
dc.contributor.authorPietiläinen, Kirsi H.en_GB
dc.contributor.authorSchumann, Gunteren_GB
dc.contributor.authorSnieder, Harolden_GB
dc.contributor.authorSternberg, Michael J. E.en_GB
dc.contributor.authorStolk, Ronald P.en_GB
dc.contributor.authorThomas, Howard C.en_GB
dc.contributor.authorThorsteinsdottir, Unnuren_GB
dc.contributor.authorUda, Manuelaen_GB
dc.contributor.authorWaeber, Gérarden_GB
dc.contributor.authorGieger, Christianen_GB
dc.contributor.authorWareham, Nicholas J.en_GB
dc.contributor.authorWaterworth, Dawn M.en_GB
dc.contributor.authorWatkins, Hughen_GB
dc.contributor.authorWhitfield, John B.en_GB
dc.contributor.authorWitteman, Jacqueline C. M.en_GB
dc.contributor.authorWolffenbuttel, Bruce H. R.en_GB
dc.contributor.authorFox, Caroline S.en_GB
dc.contributor.authorAla-Korpela, Mikaen_GB
dc.contributor.authorStefansson, Karien_GB
dc.contributor.authorVollenweider, Peteren_GB
dc.contributor.authorHeard-Costa, Nancy L.en_GB
dc.contributor.authorVölzke, Henryen_GB
dc.contributor.authorSchadt, Eric E.en_GB
dc.contributor.authorScott, Jamesen_GB
dc.contributor.authorJärvelin, Marjo-Riittaen_GB
dc.contributor.authorElliott, Paulen_GB
dc.contributor.authorKooner, Jaspal S.en_GB
dc.contributor.authorHottenga, Jouke-Janen_GB
dc.contributor.authorKühnel, Brigitteen_GB
dc.contributor.authorKumar, Vinoden_GB
dc.contributor.authorLagou, Vasilikien_GB
dc.contributor.authorLiang, Limingen_GB
dc.contributor.authorLuan, Jian'anen_GB
dc.contributor.authorVidal, Pedro Marquesen_GB
dc.contributor.authorMateo Leach, Ireneen_GB
dc.contributor.authorO'Reilly, Paul F.en_GB
dc.contributor.authorPeden, John F.en_GB
dc.contributor.authorRahmioglu, Niluferen_GB
dc.contributor.authorSoininen, Pasien_GB
dc.contributor.authorSpeliotes, Elizabeth K.en_GB
dc.contributor.authorYuan, Xinen_GB
dc.contributor.authorThorleifsson, Gudmaren_GB
dc.contributor.authorAlizadeh, Behrooz Z.en_GB
dc.contributor.authorAtwood, Larry D.en_GB
dc.contributor.authorBorecki, Ingrid B.en_GB
dc.contributor.authorBrown, Morris J.en_GB
dc.contributor.authorCharoen, Pimphenen_GB
dc.contributor.authorCucca, Francescoen_GB
dc.contributor.authorDas, Debashishen_GB
dc.contributor.authorde Geus, Eco J. C.en_GB
dc.contributor.authorDixon, Anna L.en_GB
dc.contributor.authorDöring, Angelaen_GB
dc.contributor.authorEhret, Georgen_GB
dc.contributor.authorEyjolfsson, Gudmundur I.en_GB
dc.contributor.authorFarrall, Martinen_GB
dc.contributor.authorForouhi, Nita G.en_GB
dc.contributor.authorFriedrich, Neleen_GB
dc.contributor.authorGoessling, Wolframen_GB
dc.contributor.authorGudbjartsson, Daniel F.en_GB
dc.contributor.authorHarris, Tamara B.en_GB
dc.contributor.authorHartikainen, Anna-Liisaen_GB
dc.contributor.authorHeath, Simonen_GB
dc.contributor.authorHirschfield, Gideon M.en_GB
dc.contributor.authorHofman, Alberten_GB
dc.contributor.authorHomuth, Georgen_GB
dc.contributor.authorHyppönen, Elinaen_GB
dc.contributor.authorJanssen, Harry L. A.en_GB
dc.contributor.authorJohnson, Tobyen_GB
dc.contributor.authorKangas, Antti J.en_GB
dc.contributor.authorKema, Ido P.en_GB
dc.contributor.authorKühn, Jens P.en_GB
dc.contributor.authorLai, Sandraen_GB
dc.contributor.authorLathrop, Marken_GB
dc.contributor.authorLerch, Markus M.en_GB
dc.contributor.authorLi, Yunen_GB
dc.contributor.authorLiang, T. Jakeen_GB
dc.contributor.authorLin, Jing-Pingen_GB
dc.contributor.authorLoos, Ruth J. F.en_GB
dc.contributor.authorMartin, Nicholas G.en_GB
dc.contributor.authorMoffatt, Miriam F.en_GB
dc.contributor.authorMontgomery, Grant W.en_GB
dc.contributor.authorMunroe, Patricia B.en_GB
dc.contributor.authorMusunuru, Kiranen_GB
dc.contributor.authorNakamura, Yusukeen_GB
dc.contributor.authorO'Donnell, Christopher J.en_GB
dc.contributor.authorOlafsson, Isleifuren_GB
dc.contributor.authorPenninx, Brenda W.en_GB
dc.contributor.authorPouta, Annelien_GB
dc.contributor.authorPrins, Bram P.en_GB
dc.contributor.authorProkopenko, Ingaen_GB
dc.contributor.authorPuls, Ralfen_GB
dc.contributor.authorRuokonen, Aimoen_GB
dc.contributor.authorSavolainen, Markku J.en_GB
dc.contributor.authorSchlessinger, Daviden_GB
dc.contributor.authorSchouten, Jeoffrey N. L.en_GB
dc.contributor.authorSeedorf, Udoen_GB
dc.contributor.authorSen-Chowdhry, Srijitaen_GB
dc.contributor.authorSiminovitch, Katherine A.en_GB
dc.contributor.authorSmit, Johannes H.en_GB
dc.contributor.authorSpector, Timothy D.en_GB
dc.contributor.authorTan, Wentingen_GB
dc.contributor.authorTeslovich, Tanya M.en_GB
dc.contributor.authorTukiainen, Taruen_GB
dc.contributor.authorUitterlinden, Andre G.en_GB
dc.contributor.authorVan der Klauw, Melanie M.en_GB
dc.contributor.authorVasan, Ramachandran S.en_GB
dc.contributor.authorWallace, Chrisen_GB
dc.contributor.authorWallaschofski, Henrien_GB
dc.contributor.authorWichmann, H-Erichen_GB
dc.contributor.authorWillemsen, Gonnekeen_GB
dc.contributor.authorWürtz, Peteren_GB
dc.contributor.authorXu, Chunen_GB
dc.contributor.authorYerges-Armstrong, Laura M.en_GB
dc.date.accessioned2012-07-04T08:05:43Z-
dc.date.available2012-07-04T08:05:43Z-
dc.date.issued2011-11-
dc.identifier.citationNat. Genet. 2011, 43 (11):1131-1138en_GB
dc.identifier.issn1546-1718-
dc.identifier.pmid22001757-
dc.identifier.doi10.1038/ng.970-
dc.identifier.urihttp://hdl.handle.net/10146/232031-
dc.description.abstractConcentrations 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.en_GB
dc.description.sponsorshipMajor support for the work came from European Commission (FP5, FP6 and FP7); European Science Foundation; European Science Council;en_GB
dc.language.isoenen
dc.relation.urlhttp://www.nature.com/ng/journal/v43/n11/full/ng.970.htmlen_GB
dc.rightsArchived with thanks to Nature geneticsen_GB
dc.subjectGenome-Wide Association Studyen_GB
dc.subjectGenomicsen_GB
dc.subjectLiveren_GB
dc.subjectEnzymesen_GB
dc.subjectBlooden_GB
dc.subjectHumansen_GB
dc.subjectPolymorphismen_GB
dc.subjectSingle Nucleotideen_GB
dc.subject.meshEnzymes-
dc.subject.meshGenome-Wide Association Study-
dc.subject.meshHumans-
dc.subject.meshLiver-
dc.subject.meshPolymorphism, Single Nucleotide-
dc.titleGenome-wide association study identifies loci influencing concentrations of liver enzymes in plasma.en
dc.typeArticleen
dc.identifier.journalNature Geneticsen_GB

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