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
18996923
TITLE
Associations of ADH and ALDH2 gene variation with self report alcohol reactions, consumption and dependence: an integrated analysis.
ABSTRACT
Alcohol dependence (AD) is a complex disorder with environmental and genetic origins. The role of two genetic variants in ALDH2 and ADH1B in AD risk has been extensively investigated. This study tested for associations between nine polymorphisms in ALDH2 and 41 in the seven ADH genes, and alcohol-related flushing, alcohol use and dependence symptom scores in 4597 Australian twins. The vast majority (4296) had consumed alcohol in the previous year, with 547 meeting DSM-IIIR criteria for AD. There were study-wide significant associations (P<2.3 x 10(-4)) between ADH1B-Arg48His (rs1229984) and flushing and consumption, but only nominally significant associations (P<0.01) with dependence. Individuals carrying the rs1229984 G-allele (48Arg) reported a lower prevalence of flushing after alcohol (P=8.2 x 10(-7)), consumed alcohol on more occasions (P=2.7 x 10(-6)), had a higher maximum number of alcoholic drinks in a single day (P=2.7 x 10(-6)) and a higher overall alcohol consumption (P=8.9 x 10(-8)) in the previous year than those with the less common A-allele (48His). After controlling for rs1229984, an independent association was observed between rs1042026 (ADH1B) and alcohol intake (P=4.7 x 10(-5)) and suggestive associations (P<0.001) between alcohol consumption phenotypes and rs1693482 (ADH1C), rs1230165 (ADH5) and rs3762894 (ADH4). ALDH2 variation was not associated with flushing or alcohol consumption, but was weakly associated with AD measures. These results bridge the gap between DNA sequence variation and alcohol-related behavior, confirming that the ADH1B-Arg48His polymorphism affects both alcohol-related flushing in Europeans and alcohol intake. The absence of study-wide significant effects on AD results from the low P-value required when testing multiple single nucleotide polymorphisms and phenotypes.
DATE PUBLISHED
2009 Feb 1
HISTORY
PUBSTATUS PUBSTATUSDATE
aheadofprint 2008/11/07
pubmed 2008/11/11 09:00
medline 2009/02/28 09:00
entrez 2008/11/11 09:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Macgregor S Macgregor Stuart S Genetic Epidemiology, Queensland Institute of Medical Research, Brisbane, Queensland, Australia. stuart.macgregor@qimr.edu.au
Lind PA Lind Penelope A PA
Bucholz KK Bucholz Kathleen K KK
Hansell NK Hansell Narelle K NK
Madden PA Madden Pamela A F PA
Richter MM Richter Melinda M MM
Montgomery GW Montgomery Grant W GW
Martin NG Martin Nicholas G NG
Heath AC Heath Andrew C AC
Whitfield JB Whitfield John B JB
INVESTIGATORS
JOURNAL
VOLUME: 18
ISSUE: 3
TITLE: Human molecular genetics
ISOABBREVIATION: Hum. Mol. Genet.
YEAR: 2009
MONTH: Feb
DAY: 1
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
Twin Study
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
AA013326 NIAAA NIH HHS United States
AA014041 NIAAA NIH HHS United States
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
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adult
Aged
Aged, 80 and over
Alcohol Dehydrogenase metabolism
Alcohol Drinking metabolism
Alcoholism psychology
Aldehyde Dehydrogenase metabolism
Australia metabolism
Diseases in Twins genetics
European Continental Ancestry Group genetics
Female genetics
Flushing metabolism
Genetic Variation metabolism
Humans metabolism
Male metabolism
Middle Aged metabolism
Polymorphism, Single Nucleotide metabolism
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
EC 1.1.1.1 ADH1B protein, human
EC 1.1.1.1 Alcohol Dehydrogenase
EC 1.2.1.3 ALDH2 protein, human
EC 1.2.1.3 Aldehyde Dehydrogenase
OTHER ID's
OTHERID SOURCE
PMC2722191 NLM