@article{ae676edba0b44df2b395984ed9bca262,
title = "Loci affecting gamma-glutamyl transferase in adults and adolescents show age × SNP interaction and cardiometabolic disease associations",
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.",
author = "Middelberg, {Rita P.} and Beben Benyamin and {de Moor}, {Marleen H.M.} and Warrington, {Nicole M.} and Scott Gordon and Henders, {Anjali K.} and Medland, {Sarah E.} and Nyholt, {Dale R.} and {de Geus}, {Eco J.C.} and Hottenga, {Jouke J.} and Gonneke Willemsen and Beilin, {Lawrence J.} and Mori, {Trevor A.} and Wright, {Margaret J.} and Heath, {Andrew C.} and Madden, {Pamela A.F.} and Boomsma, {Dorret I.} and Pennell, {Craig E.} and Montgomery, {Grant W.} and Martin, {Nicholas G.} and Whitfield, {John B.}",
note = "Funding Information: The Australian studies at QIMR were supported by NIH grants AA07535, AA07728, AA13320, AA13321, AA13326, AA14041, AA11998, AA17688, DA012854, DA019951; by grants from the Australian National Health and Medical Research Council (241944, 339462, 389927, 389875, 389891, 389892, 389938, 442915, 442981, 496739, 552485, 552498); from the Australian Research Council (A7960034, A79906588, A79801419, DP0770096, DP0212016, DP0343921); and the FP-5 GenomEUtwin Project (QLG2-CT-2002-01254). Genotyping at CIDR was supported by grant AA13320 to the late Richard Todd, PhD, MD. R.P.M., S.E.M., D.R.N., and G.W.M. are supported by the National Health and Medical Research Council (NHMRC) Fellowship Scheme. The authors gratefully acknowledge the NH&MRC for their long-term contribution to funding the Raine Study over the last 20 years and also the following Institutions for providing funding for Core Management of the Raine Study: The University of Western Australia; Raine Medical Research Foundation; UWA Faculty of Medicine, Dentistry and Health Sciences; The Telethon Institute for Child Health Research; and the Women and Infants Research Foundation. The authors gratefully acknowledge the assistance of the Western Australian DNA Bank (National Health and Medical Research Council of Australia National Enabling Facility). The authors also acknowledge the support of the National Health and Medical Research Council of Australia (Grant ID 572613 and ID 003209) and the Canadian Institutes of Health Research (Grant ID 166067). For the Netherlands studies, funding was obtained from the Netherlands Organization for Scientific Research (NWO: MagW/ZonMW) Grants 904-61-090; 985-10-002; 904-61-193; 480-04-004; 400-05-717; 911-09-032; Addiction-31160008; Spinozapre-mie (SPI 56-464-14192); CMSB: Center for Medical Systems Biology (NWO Genomics); NBIC/BioAssist/RK/ 2008.024; BBMRI-NL: Biobanking and Biomolecular Resources Research Infrastructure; the VU University: Institute for Health and Care Research (EMGO+) and Neuroscience Campus Amsterdam (NCA); the European Science Foundation (ESF): EU/QLRT-2001-01254; European Community{\textquoteright}s Seventh Framework Program (FP7/2007-2013): ENGAGE (HEALTH-F4-2007-201413); the European Science Council (ERC) Genetics of Mental Illness (230374); Rutgers University Cell and DNA Repository cooperative agreement (NIH U24 MH068457-06); Collaborative study of the genetics of DZ twinning (NIH R01D0042157-01A); and the Genetic Association Information Network, a public– private partnership between the NIH and Pfizer Inc., Affyme-trix Inc. and Abbott Laboratories. M.H.M.M. is financially supported by NWO (VENI-grant 016-115-035). Funding Information: For the Raine study, the authors are grateful to the Raine Foundation, to the study participants and their families, and to the research staff for cohort coordination and data collection. We gratefully acknowledge the assistance of the Telethon Institute for Child Health Research and the Raine Medical Research Foundation of the University of Western Australia.",
year = "2012",
month = jan,
doi = "10.1093/hmg/ddr478",
language = "English",
volume = "21",
pages = "446--455",
journal = "Human molecular genetics",
issn = "0964-6906",
number = "2",
}