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

Chambers, John C. and Zhang, Weihua and Sehmi, Joban and Li, Xinzhong and Wass, Mark N. and Van der Harst, Pim and Holm, Hilma and Sanna, Serena and Kavousi, Maryam and Baumeister, Sebastian E. and Coin, Lachlan J. and Deng, Guohong and Gieger, Christian and Heard-Costa, Nancy L. and Hottenga, Jouke-Jan and Kühnel, Brigitte and Kumar, Vinod and Lagou, Vasiliki and Liang, Liming and Luan, Jian'an and Vidal, Pedro Marques and Mateo Leach, Irene and O'Reilly, Paul F. and Peden, John F. and Rahmioglu, Nilufer and Soininen, Pasi and Speliotes, Elizabeth K. and Yuan, Xin and Thorleifsson, Gudmar and Alizadeh, Behrooz Z. and Atwood, Larry D. and Borecki, Ingrid B. and Brown, Morris J. and Charoen, Pimphen and Cucca, Francesco and Das, Debashish and de Geus, Eco J. C. and Dixon, Anna L. and Döring, Angela and Ehret, Georg and Eyjolfsson, Gudmundur I. and Farrall, Martin and Forouhi, Nita G. and Friedrich, Nele and Goessling, Wolfram and Gudbjartsson, Daniel F. and Harris, Tamara B. and Hartikainen, Anna-Liisa and Heath, Simon and Hirschfield, Gideon M. and Hofman, Albert and Homuth, Georg and Hyppönen, Elina and Janssen, Harry L. A. and Johnson, Toby and Kangas, Antti J. and Kema, Ido P. and Kühn, Jens P. and Lai, Sandra and Lathrop, Mark and Lerch, Markus M. and Li, Yun and Liang, T. Jake and Lin, Jing-Ping and Loos, Ruth J. F. and Martin, Nicholas G. and Moffatt, Miriam F. and Montgomery, Grant W. and Munroe, Patricia B. and Musunuru, Kiran and Nakamura, Yusuke and O'Donnell, Christopher J. and Olafsson, Isleifur and Penninx, Brenda W. and Pouta, Anneli and Prins, Bram P. and Prokopenko, Inga and Puls, Ralf and Ruokonen, Aimo and Savolainen, Markku J. and Schlessinger, David and Schouten, Jeoffrey N. L. and Seedorf, Udo and Sen-Chowdhry, Srijita and Siminovitch, Katherine A. and Smit, Johannes H. and Spector, Timothy D. and Tan, Wenting and Teslovich, Tanya M. and Tukiainen, Taru and Uitterlinden, Andre G. and Van der Klauw, Melanie M. and Vasan, Ramachandran S. and Wallace, Chris and Wallaschofski, Henri and Wichmann, H-Erich and Willemsen, Gonneke and Würtz, Peter and Xu, Chun and Yerges-Armstrong, Laura M. and Alcohol Genome-wide Association Consortium, and Diabetes Genetics Replication, and Meta-analyses Study, and Genetic Investigation of Anthropometric Traits Consortium, and Global Lipids Genetics Consortium, and Genetics of Liver Disease Consortium, and International Consortium for Blood Pressure, and Meta-analyses of Glucose, and Insulin-Related Traits Consortium, and Abecasis, Goncalo R. and Ahmadi, Kourosh R. and Boomsma, Dorret I. and Caulfield, Mark and Cookson, William O. and van Duijn, Cornelia M. and Froguel, Philippe and Matsuda, Koichi and McCarthy, Mark I. and Meisinger, Christa and Mooser, Vincent and Pietiläinen, Kirsi H. and Schumann, Gunter and Snieder, Harold and Sternberg, Michael J. E. and Stolk, Ronald P. and Thomas, Howard C. and Thorsteinsdottir, Unnur and Uda, Manuela and Waeber, Gérard and Wareham, Nicholas J. and Waterworth, Dawn M. and Watkins, Hugh and Whitfield, John B. and Witteman, Jacqueline C. M. and Wolffenbuttel, Bruce H. R. and Fox, Caroline S. and Ala-Korpela, Mika and Stefansson, Kari and Vollenweider, Peter and Völzke, Henry and Schadt, Eric E. and Scott, James and Järvelin, Marjo-Riitta and Elliott, Paul and Kooner, Jaspal S.. (2011) Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma. Nature Genetics, 43 (11). pp. 1131-1138.

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Official URL: https://edoc.unibas.ch/81762/

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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.
Faculties and Departments:03 Faculty of Medicine
09 Associated Institutions > Institute of Molecular and Clinical Ophthalmology Basel (IOB)
UniBasel Contributors:Rivolta, Carlo
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Nature Publishing Group
ISSN:1061-4036
e-ISSN:1546-1718
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
edoc DOI:
Last Modified:12 May 2021 11:55
Deposited On:12 May 2021 11:55

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