Shin, D.M., Zhao, X.S., Zeng, W., Mozhayeva, M. A gene encoding a P-type ATPase mutated in two forms of hereditary cholestasis. Genetic Loci associated with C-reactive protein levels and risk of coronary heart disease. Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes. Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis. New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. Mouse glycosylphosphatidylinositol-specific phospholipase D (Gpld1) characterization. Tissue-specific loss of fucosylated glycolipids in mice with targeted deletion of alpha(1,2)fucosyltransferase genes. Atp8b1 deficiency in mice reduces resistance of the canalicular membrane to hydrophobic bile salts and impairs bile salt transport. A second generation human haplotype map of over 3.1 million SNPs. Genome-wide association study of hematological and biochemical traits in a Japanese population. Population-based genome-wide association studies reveal six loci influencing plasma levels of liver enzymes. Estimation of the multiple testing burden for genomewide association studies of nearly all common variants. Evaluation and management of obesity-related nonalcoholic fatty liver disease. Epidemiology and genetic epidemiology of the liver function test proteins. Idiosyncratic liver injury: challenges and approaches. Elevated serum alanine aminotransferase activity and calculated risk of coronary heart disease in the United States. Ioannou, G.N., Weiss, N.S., Boyko, E.J., Mozaffarian, D. ![]() Elevated alanine aminotransferase predicts new-onset type 2 diabetes independently of classical risk factors, metabolic syndrome, and C-reactive protein in the west of Scotland coronary prevention study. Diagnostic value of serum γ-glutamyl transferase isoenzyme for hepatocellular carcinoma: a 10-year study. Decreased survival of subjects with elevated liver function tests during a 28-year follow-up. Evaluation of abnormal liver-enzyme results in asymptomatic patients. Our results provide new insight into genetic mechanisms and pathways influencing markers of liver function. 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, MICA元 and ZNF827). We used functional genomic approaches including metabonomic profiling and gene expression analyses to identify probable candidate genes at these regions. 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). Nature Genetics volume 43, pages 1131–1138 ( 2011) Cite this articleĬoncentrations of liver enzymes in plasma are widely used as indicators of liver disease.
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