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

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.

SUBMITTER: Chambers JC 

PROVIDER: S-EPMC3482372 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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

Chambers John C JC   Zhang Weihua W   Sehmi Joban J   Li Xinzhong X   Wass Mark N MN   Van der Harst Pim P   Holm Hilma H   Sanna Serena S   Kavousi Maryam M   Baumeister Sebastian E SE   Coin Lachlan J LJ   Deng Guohong G   Gieger Christian C   Heard-Costa Nancy L NL   Hottenga Jouke-Jan JJ   Kühnel Brigitte B   Kumar Vinod V   Lagou Vasiliki V   Liang Liming L   Luan Jian'an J   Vidal Pedro Marques PM   Mateo Leach Irene I   O'Reilly Paul F PF   Peden John F JF   Rahmioglu Nilufer N   Soininen Pasi P   Speliotes Elizabeth K EK   Yuan Xin X   Thorleifsson Gudmar G   Alizadeh Behrooz Z BZ   Atwood Larry D LD   Borecki Ingrid B IB   Brown Morris J MJ   Charoen Pimphen P   Cucca Francesco F   Das Debashish D   de Geus Eco J C EJ   Dixon Anna L AL   Döring Angela A   Ehret Georg G   Eyjolfsson Gudmundur I GI   Farrall Martin M   Forouhi Nita G NG   Friedrich Nele N   Goessling Wolfram W   Gudbjartsson Daniel F DF   Harris Tamara B TB   Hartikainen Anna-Liisa AL   Heath Simon S   Hirschfield Gideon M GM   Hofman Albert A   Homuth Georg G   Hyppönen Elina E   Janssen Harry L A HL   Johnson Toby T   Kangas Antti J AJ   Kema Ido P IP   Kühn Jens P JP   Lai Sandra S   Lathrop Mark M   Lerch Markus M MM   Li Yun Y   Liang T Jake TJ   Lin Jing-Ping JP   Loos Ruth J F RJ   Martin Nicholas G NG   Moffatt Miriam F MF   Montgomery Grant W GW   Munroe Patricia B PB   Musunuru Kiran K   Nakamura Yusuke Y   O'Donnell Christopher J CJ   Olafsson Isleifur I   Penninx Brenda W BW   Pouta Anneli A   Prins Bram P BP   Prokopenko Inga I   Puls Ralf R   Ruokonen Aimo A   Savolainen Markku J MJ   Schlessinger David D   Schouten Jeoffrey N L JN   Seedorf Udo U   Sen-Chowdhry Srijita S   Siminovitch Katherine A KA   Smit Johannes H JH   Spector Timothy D TD   Tan Wenting W   Teslovich Tanya M TM   Tukiainen Taru T   Uitterlinden Andre G AG   Van der Klauw Melanie M MM   Vasan Ramachandran S RS   Wallace Chris C   Wallaschofski Henri H   Wichmann H-Erich HE   Willemsen Gonneke G   Würtz Peter P   Xu Chun C   Yerges-Armstrong Laura M LM   Abecasis Goncalo R GR   Ahmadi Kourosh R KR   Boomsma Dorret I DI   Caulfield Mark M   Cookson William O WO   van Duijn Cornelia M CM   Froguel Philippe P   Matsuda Koichi K   McCarthy Mark I MI   Meisinger Christa C   Mooser Vincent V   Pietiläinen Kirsi H KH   Schumann Gunter G   Snieder Harold H   Sternberg Michael J E MJ   Stolk Ronald P RP   Thomas Howard C HC   Thorsteinsdottir Unnur U   Uda Manuela M   Waeber Gérard G   Wareham Nicholas J NJ   Waterworth Dawn M DM   Watkins Hugh H   Whitfield John B JB   Witteman Jacqueline C M JC   Wolffenbuttel Bruce H R BH   Fox Caroline S CS   Ala-Korpela Mika M   Stefansson Kari K   Vollenweider Peter P   Völzke Henry H   Schadt Eric E EE   Scott James J   Järvelin Marjo-Riitta MR   Elliott Paul P   Kooner Jaspal S JS  

Nature genetics 20111016 11

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  ...[more]