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

• 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
• Subjects: Biochemistry, Genetics and Molecular Biology
• Online Access: https://repository.li.mahidol.ac.th/handle/123456789/11450
• Institution: Mahidol University

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.