Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
22010049
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.
The Author 2011. Published by Oxford University Press. All rights reserved.
DATE PUBLISHED
2012 Jan 15
HISTORY
PUBSTATUS PUBSTATUSDATE
aheadofprint 2011/10/18
aheadofprint 2011/11/01
entrez 2011/10/20 06:00
pubmed 2011/10/20 06:00
medline 2012/04/27 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Middelberg RP Middelberg Rita P RP Queensland Institute of Medical Research, Brisbane, Australia.
Benyamin B Benyamin Beben B
de Moor MH de Moor Marleen H M MH
Warrington NM Warrington Nicole M NM
Gordon S Gordon Scott S
Henders AK Henders Anjali K AK
Medland SE Medland Sarah E SE
Nyholt DR Nyholt Dale R DR
de Geus EJ de Geus Eco J C EJ
Hottenga JJ Hottenga Jouke J JJ
Willemsen G Willemsen Gonneke G
Beilin LJ Beilin Lawrence J LJ
Mori TA Mori Trevor A TA
Wright MJ Wright Margaret J MJ
Heath AC Heath Andrew C AC
Madden PA Madden Pamela A F PA
Boomsma DI Boomsma Dorret I DI
Pennell CE Pennell Craig E CE
Montgomery GW Montgomery Grant W GW
Martin NG Martin Nicholas G NG
Whitfield JB Whitfield John B JB
INVESTIGATORS
JOURNAL
VOLUME: 21
ISSUE: 2
TITLE: Human molecular genetics
ISOABBREVIATION: Hum. Mol. Genet.
YEAR: 2012
MONTH: Jan
DAY: 15
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1460-2083
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Hum Mol Genet
COUNTRY: England
ISSNLINKING: 0964-6906
NLMUNIQUEID: 9208958
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
166067 Canadian Institutes of Health Research Canada
AA07535 NIAAA NIH HHS United States
AA07728 NIAAA NIH HHS United States
AA11998 NIAAA NIH HHS United States
AA13320 NIAAA NIH HHS United States
AA13321 NIAAA NIH HHS United States
AA13326 NIAAA NIH HHS United States
AA14041 NIAAA NIH HHS United States
AA17688 NIAAA NIH HHS United States
DA012854 NIDA NIH HHS United States
DA019951 NIDA NIH HHS United States
K05 AA017688 NIAAA NIH HHS United States
R01D0042157-01A PHS HHS United States
U24 MH068457-06 NIMH NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adolescent
Adult
Age Factors
Alleles
Genetic Heterogeneity
Genome-Wide Association Study
Heart Diseases genetics
Humans genetics
Metabolic Diseases genetics
Polymorphism, Single Nucleotide genetics
gamma-Glutamyltransferase genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
EC 2.3.2.2 gamma-Glutamyltransferase
OTHER ID's
OTHERID SOURCE
PMC3276286 NLM