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

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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
Deng, Guohong
Gieger, Christian
Heard-Costa, Nancy L
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
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
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
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
Völzke, Henry
Schadt, Eric E
Scott, James
Järvelin, Marjo-Riitta
Elliott, Paul
Kooner, Jaspal S
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Issue Date
2011-11

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Citation
Nat. Genet. 2011, 43(11):1131-8
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.
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To access publisher full text version of this article. Please click on the hyperlink in Additional Links field.
Additional Links
http://dx.doi.org/10.1038/ng.970
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Archived with thanks to Nature genetics
ae974a485f413a2113503eed53cd6c53
10.1038/ng.970
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English Journal Articles (Peer Reviewed)

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