Loci affecting gamma-glutamyl transferase in adults and adolescents show age × SNP interaction and cardiometabolic disease associations
Date
2012
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Middelberg, R.P.
Benyamin, B.
de Moor, M.H.M.
Warrington, N.M.
Whitfield, J.B.
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Human Molecular Genetics, 2012; 21(2):446-455
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Abstract
Serum gamma-glutamyl transferase (GGT) activity is a marker of liver disease which is also prospectively associated with the risk of all-cause mortality, cardiovascular disease, type 2 diabetes and cancers. We have discovered novel loci affecting GGT in a genome-wide association study (rs1497406 in an intergenic region of chromosome 1, P = 3.9 × 10 -8 ; rs944002 in C14orf73 on chromosome 14, P = 4.7 × 10 -13 ; rs340005 in RORA on chromosome 15, P = 2.4 × 10 -8 ), and a highly significant heterogeneity between adult and adolescent results at the GGT1 locus on chromosome 22 (maximum P HET = 5.6 × 10 -12 at rs6519520). Pathway analysis of significant and suggestive single-nucleotide polymorphism associations showed significant overlap between genes affecting GGT and those affecting common metabolic and inflammatory diseases, and identified the hepatic nuclear factor (HNF) family as controllers of a network of genes affecting GGT. Our results reinforce the disease associations of GGT and demonstrate that control by the GGT1 locus varies with age.
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Copyright 2011 The authors
Access Condition Notes: This article is free to read online