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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19183129
TITLE
Can we identify genes for alcohol consumption in samples ascertained for heterogeneous purposes?
ABSTRACT
BACKGROUND NlmCategory: BACKGROUND
Previous studies have identified evidence of genetic influence on alcohol use in samples selected to be informative for alcoholism research. However, there are a growing number of genome-wide association studies (GWAS) using samples unselected for alcohol consumption (i.e., selected on other traits and forms of psychopathology), which nevertheless assess consumption as a risk factor. Is it reasonable to expect that genes contributing to variation in alcohol consumption can be identified in such samples?
METHODS NlmCategory: METHODS
An exploratory approach was taken to determine whether linkage analyses for heaviness of alcohol consumption, using a sample collected for heterogeneous purposes, could replicate previous findings. Quantity and frequency measures of consumption were collected in telephone interviews from community samples. These measures, and genotyping, were available for 5,441 individuals (5,067 quasi-independent sibling pairs). For 1,533 of these individuals, data were collected on 2 occasions, about 8.2 years apart, providing 2 datasets that maximize data collected at either a younger or an older age. Analyses were conducted to address the question of whether age and heavier levels of alcohol consumption effects outcome. Linkage results were compared in the younger and older full samples, and with samples in which approximately 10, 20, and 40 of drinkers from the lower end of the distribution of alcohol consumption were dropped.
RESULTS NlmCategory: RESULTS
Linkage peaks varied for the age differentiated samples and for percentage of light drinkers retained. Larger peaks (LOD scores >2.0) were typically found in regions previously identified in linkage studies and/or containing proposed candidate genes for alcoholism including AGT, CARTPT, OPRD1, PIK3R1, and PDYN.
CONCLUSIONS NlmCategory: CONCLUSIONS
The results suggest that GWAS assessing alcohol consumption as a covariate for other conditions will have some success in identifying genes contributing to consumption-related variation. However, sample characteristics, such as participant age, and trait distribution, may have substantial effects on the strength of the genetic signal. These results can inform forthcoming GWAS where the same restrictions apply.
DATE PUBLISHED
2009 Apr
HISTORY
PUBSTATUS PUBSTATUSDATE
aheadofprint 2009/01/22
entrez 2009/02/03 09:00
pubmed 2009/02/03 09:00
medline 2009/07/08 09:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Hansell NK Hansell Narelle K NK Genetic Epidemiology, Queensland Institute of Medical Research, Brisbane, Queensland, Australia. Narelle.Hansell@qimr.edu.au
Agrawal A Agrawal Arpana A
Whitfield JB Whitfield John B JB
Morley KI Morley Katherine I KI
Gordon SD Gordon Scott D SD
Lind PA Lind Penelope A PA
Pergadia ML Pergadia Michele L ML
Montgomery GW Montgomery Grant W GW
Madden PA Madden Pamela A F PA
Todd RD Todd Richard D RD
Heath AC Heath Andrew C AC
Martin NG Martin Nicholas G NG
INVESTIGATORS
JOURNAL
VOLUME: 33
ISSUE: 4
TITLE: Alcoholism, clinical and experimental research
ISOABBREVIATION: Alcohol. Clin. Exp. Res.
YEAR: 2009
MONTH: Apr
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1530-0277
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Alcohol Clin Exp Res
COUNTRY: England
ISSNLINKING: 0145-6008
NLMUNIQUEID: 7707242
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
AA014041 NIAAA NIH HHS United States
AA07728 NIAAA NIH HHS United States
AA10248 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
DA019951 NIDA NIH HHS United States
DA023668 NIDA NIH HHS United States
DA12854 NIDA NIH HHS United States
K08 DA019951 NIDA NIH HHS United States
K08 DA019951-04 NIDA NIH HHS United States
P50 AA011998 NIAAA NIH HHS United States
P50 AA011998-10 NIAAA NIH HHS United States
R01 AA010249 NIAAA NIH HHS United States
R01 AA010249-04 NIAAA NIH HHS United States
R01 AA013320-04 NIAAA NIH HHS United States
R01 AA013321 NIAAA NIH HHS United States
R01 AA013321-05 NIAAA NIH HHS United States
R01 AA013326-05 NIAAA NIH HHS United States
R01 AA014041-05 NIAAA NIH HHS United States
R01 DA012854 NIDA NIH HHS United States
R01 DA012854-05 NIDA NIH HHS United States
R01 DA023668 NIDA NIH HHS United States
R01 DA023668-02 NIDA NIH HHS United States
R37 AA007728 NIAAA NIH HHS United States
R37 AA007728-20 NIAAA NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adult
Age Factors
Aged
Aged, 80 and over
Alcohol Drinking genetics
Angiotensinogen genetics
Australia genetics
Data Collection genetics
Enkephalins genetics
Female genetics
Genetic Heterogeneity genetics
Genetic Linkage genetics
Genetic Predisposition to Disease genetics
Genotype genetics
Humans genetics
Interviews as Topic genetics
Linear Models genetics
Male genetics
Middle Aged genetics
Protein Precursors genetics
Receptors, Opioid, delta genetics
Young Adult genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 AGT protein, human
0 Enkephalins
0 OPRD1 protein, human
0 Protein Precursors
0 Receptors, Opioid, delta
11002-13-4 Angiotensinogen
93443-35-7 preproenkephalin
OTHER ID's
OTHERID SOURCE
NIHMS314587 NLM
PMC3164813 NLM