Genetic Epidemiology, Psychiatric Genetics, Asthma 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
16184481
TITLE
Genetic time-series analysis identifies a major QTL for in vivo alcohol metabolism not predicted by in vitro studies of structural protein polymorphism at the ADH1B or ADH1C loci.
ABSTRACT
After ingestion of a standardized dose of ethanol, alcohol concentrations were assessed, over 3.5 hours from blood (six readings) and breath (10 readings) in a sample of 412 MZ and DZ twins who took part in an Alcohol Challenge Twin Study (ACTS). Nearly all participants were subsequently genotyped on two polymorphic SNPs in the ADH1B and ADH1C loci known to affect in vitro ADH activity. In the DZ pairs, 14 microsatellite markers covering a 20.5 cM region on chromosome 4 that includes the ADH gene family were assessed, Variation in the timed series of autocorrelated blood and breath alcohol readings was studied using a bivariate simplex design. The contribution of a quantitative trait locus (QTL) or QTL's linked to the ADH region was estimated via a mixture of likelihoods weighted by identity-by-descent probabilities. The effects of allelic substitution at the ADH1B and ADH1C loci were estimated in the means part of the model simultaneously with the effects sex and age. There was a major contribution to variance in alcohol metabolism due to a QTL which accounted for about 64% of the additive genetic covariation common to both blood and breath alcohol readings at the first time point. No effects of the ADH1B*47His or ADH1C*349Ile alleles on in vivo metabolism were observed, although these have been shown to have major effects in vitro. This implies that there is a major determinant of variation for in vivo alcohol metabolism in the ADH region that is not accounted for by these polymorphisms. Earlier analyses of these data suggested that alcohol metabolism is related to drinking behavior and imply that this QTL may be protective against alcohol dependence.
DATE PUBLISHED
2005 Sep
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2004/06/03
accepted 2005/02/22
pubmed 2005/09/27 09:00
medline 2006/01/24 09:00
entrez 2005/09/27 09:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Birley AJ Birley A J AJ Queensland Institute of Medical Research and Joint Genetics Program, University of Queensland, 300 Herston Road, Herston, Brisbane, QLD, 4029, Australia. andrewBi@qimr.edu.au
Whitfield JB Whitfield J B JB
Neale MC Neale M C MC
Duffy DL Duffy D L DL
Heath AC Heath A C AC
Boomsma DI Boomsma D I DI
Martin NG Martin N G NG
INVESTIGATORS
JOURNAL
VOLUME: 35
ISSUE: 5
TITLE: Behavior genetics
ISOABBREVIATION: Behav. Genet.
YEAR: 2005
MONTH: Sep
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Print
ISSN: 0001-8244
ISSNTYPE: Print
MEDLINE JOURNAL
MEDLINETA: Behav Genet
COUNTRY: United States
ISSNLINKING: 0001-8244
NLMUNIQUEID: 0251711
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Clinical Trial
Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Twin Study
COMMENTS AND CORRECTIONS
GRANTS
GRANTID AGENCY COUNTRY
AA013321 NIAAA NIH HHS United States
AA013326 NIAAA NIH HHS United States
AA014041 NIAAA NIH HHS United States
AA077281 NIAAA NIH HHS United States
MH-65322 NIMH NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adolescent
Adult
Age Factors
Alcohol Dehydrogenase genetics
Alcoholism genetics
Chromosomes, Human, Pair 14 genetics
Diseases in Twins genetics
Ethanol blood
Female blood
Genetic Linkage blood
Genetic Variation blood
Haplotypes blood
Humans blood
Male blood
Microsatellite Repeats blood
Models, Genetic blood
Polymorphism, Single Nucleotide genetics
Quantitative Trait Loci genetics
Sex Factors genetics
Twins, Dizygotic genetics
Twins, Monozygotic genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
3K9958V90M Ethanol
EC 1.1.1.1 ADH1B protein, human
EC 1.1.1.1 ADH1C protein, human
EC 1.1.1.1 Alcohol Dehydrogenase
OTHER ID's