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, Nicole M., Gordon, Scott, Henders, Anjali K., Medland, Sarah E., Nyholt, Dale R., de Geus, Eco J. C., Hottenga, Jouke J., 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. and 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: 446-455. doi:10.1093/hmg/ddr478


Author Middelberg, Rita P.
Benyamin, Beben
de Moor, Marleen H. M.
Warrington, Nicole M.
Gordon, Scott
Henders, Anjali K.
Medland, Sarah E.
Nyholt, Dale R.
de Geus, Eco J. C.
Hottenga, Jouke J.
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.
Title Loci affecting gamma-glutamyl transferase in adults and adolescents show age x SNP interaction and cardiometabolic disease associations
Journal name Human Molecular Genetics   Check publisher's open access policy
ISSN 0964-6906
1460-2083
Publication date 2012-01
Year available 2011
Sub-type Article (original research)
DOI 10.1093/hmg/ddr478
Volume 21
Issue 2
Start page 446
End page 455
Total pages 10
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Collection year 2013
Language eng
Formatted 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 PHET = 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.
Keyword Genome-wide association
Gene expression
Liver enzymes
Risk factors
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status Non-UQ
Additional Notes Published online 18 October 2011

Document type: Journal Article
Sub-type: Article (original research)
Collection: Non HERDC
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 13 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 15 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Fri, 17 Aug 2012, 19:45:56 EST by System User on behalf of Queensland Brain Institute