American Journal of Epidemiology Advance Access originally published online on November 7, 2007
American Journal of Epidemiology 2008 167(2):125-138; doi:10.1093/aje/kwm281
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Meta-Analysis of the Association of the Taq1A Polymorphism with the Risk of Alcohol Dependency: A HuGE Gene-Disease Association Review
1 School of Health and Social Care, Oxford Brookes University, Marston, United Kingdom
2 Clinical Trials Unit, Warwick Medical School, University of Warwick, Coventry, United Kingdom
3 Social, Genetic and Developmental Psychiatry Centre (MRC), Institute of Psychiatry, King's College London, London, United Kingdom
Correspondence to Dr. Lesley Smith, School of Health and Social Care, Oxford Brookes University, Jack Straws Lane, Marston, OX3 0FL, United Kingdom (e-mail: lesleysmith{at}brookes.ac.uk).
Received for publication February 22, 2007. Accepted for publication September 6, 2007.
The human dopamine 2 receptor Taq1A allele has been implicated as a vulnerability factor for alcohol dependence in a number of studies and reviews. To determine whether this allele is associated with alcoholism, the authors conducted a Human Genome Epidemiology review and meta-analysis. Forty-four studies with 9,382 participants were included. An odds ratio of 1.38 (95% confidence interval: 1.20, 1.58; heterogeneity, 50.5%) was found for the A1A1 + A1A2 versus the A2A2 genotype. Sensitivity analyses suggested lack of ethnic matching as a possible source of heterogeneity; a small, significant association was detected in studies with ethnic-matched controls (odds ratio = 1.26, 95% confidence interval: 1.02, 1.56; heterogeneity, 37%). Significant associations were also found in analyses restricted to studies reporting use of blinding and those with adequate screening of controls for alcohol dependency. For the A1A1 versus the A1A2 + A2A2 genotype, the odds ratio was 1.22 (95% confidence interval: 1.05, 1.43; heterogeneity, 0%). Sensitivity analyses on groups of studies reporting use of ethnic-matched controls and those that screened controls for alcohol dependency still showed significant associations. The relatively small effect for the association of the A1 allele, or another genetic variant linked to it, with alcohol dependence indicates a multigene causality for this complex disorder.
alleles; association; dependency (psychology); DRD2; epidemiology; meta-analysis; review (gene-disease association); Taq1A
Abbreviations: CI, confidence interval; DRD2, dopamine receptor D2 gene; GABA,
-aminobutyric acid; OR, odds ratio
Editor's note: This paper is also available on the website of the Human Genome Epidemiology Network (http://www.cdc.gov/genomics/hugenet/).
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