Can We Identify Genes For Alcohol Consumption In Samples Ascertained For Heterogeneous Purposes?

Narelle K. Hansell, Arpana Agrawal, John B. Whitfield, Katherine I. Morley, Scott D. Gordon, Penelope A. Lind, Michele L. Pergadia, Grant W. Montgomery, Pamela A. F. Madden, Richard D. Todd, Andrew C. Heath and Nicholas G. Martin (2009) Can We Identify Genes For Alcohol Consumption In Samples Ascertained For Heterogeneous Purposes?. Alcoholism: Clinical and Experimental Research, 33 4: 729-739. doi:10.1111/j.1530-0277.2008.00890.x

Author Narelle K. Hansell
Arpana Agrawal
John B. Whitfield
Katherine I. Morley
Scott D. Gordon
Penelope A. Lind
Michele L. Pergadia
Grant W. Montgomery
Pamela A. F. Madden
Richard D. Todd
Andrew C. Heath
Nicholas G. Martin
Title Can We Identify Genes For Alcohol Consumption In Samples Ascertained For Heterogeneous Purposes?
Journal name Alcoholism: Clinical and Experimental Research   Check publisher's open access policy
ISSN 0145-6008
Publication date 2009-01-22
Year available 2009
Sub-type Article (original research)
DOI 10.1111/j.1530-0277.2008.00890.x
Volume 33
Issue 4
Start page 729
End page 739
Total pages 11
Editor Harriet de Wit
Ivan Diamond
Place of publication United States
Publisher Wiley-Blackwell Publishing
Collection year 2010
Language eng
Subject C1
Formatted abstract
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: 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: 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.

: 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.

Keyword Alcohol Consumption
Linkage Analysis
Q-Index Code C1
Q-Index Status Confirmed Code

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 6 times in Thomson Reuters Web of Science Article | Citations
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Created: Wed, 24 Mar 2010, 17:48:33 EST by Amanda Jones on behalf of Medicine - Royal Brisbane and Women's Hospital