Loci affecting gamma-glutamyl transferase in adults and adolescents show age x SNP interaction and cardiometabolic disease associations

Middelberg, Rita P., Benyamin, Beben, de Moor, Marleen H.M., Warrington, Nichole M., Gordon, Scott, Henders, Anjali K., Medland, Sarah E., Nyholt, Dale R., de Geus, Eco J.C., Hottenga, Jouke-Jan, Willemsen, Gonneke, Beilin, Lawrence J., Mori, Trevor A., Wright, Margaret J., Heath, Andrew C., Madden, Pamela A.F., Boomsma, Dorret I., Pennell, Craig E., Montgomery, Grant W., Martin, Nicholas G., & Whitfield, John B. (2012) Loci affecting gamma-glutamyl transferase in adults and adolescents show age x SNP interaction and cardiometabolic disease associations. Human Molecular Genetics, 21(2), pp. 446-455.

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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 x 10(-8); rs944002 in C14orf73 on chromosome 14, P = 4.7 x 10(-13); rs340005 in RORA on chromosome 15, P = 2.4 x 10(-8)), and a highly significant heterogeneity between adult and adolescent results at the GGT1 locus on chromosome 22 (maximum P(HET) = 5.6 x 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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16 citations in Scopus
14 citations in Web of Science®
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ID Code: 91841
Item Type: Journal Article
Refereed: Yes
Keywords: Adolescent, Adult, Age Factors, Alleles, Genetic Heterogeneity, Genome-Wide Association Study, Heart Diseases/*genetics, Humans, Metabolic Diseases/*genetics, *Polymorphism, Single Nucleotide, gamma-Glutamyltransferase/*genetics
DOI: 10.1093/hmg/ddr478
ISSN: 1460-2083
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Deposited On: 13 Jan 2016 03:30
Last Modified: 14 Jan 2016 00:22

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