Variation in GABRA2 Predicts Drinking Behavior in Project MATCH Subjects

Authors

  • Lance O. Bauer,

    1. From the Department of Psychiatry, Alcohol Research Center, University of Connecticut School of Medicine (LOB, JC, HRK), Farmington, Connecticut; Department of Statistics, University of Connecticut (OH, SD), Storrs, Connecticut; Department of Psychiatry, Division of Human Genetics in Psychiatry, Yale University School of Medicine (JG), VA Connecticut, West Haven, Connecticut; and Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina (RA), Charleston, South Carolina.
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  • Jonathan Covault,

    1. From the Department of Psychiatry, Alcohol Research Center, University of Connecticut School of Medicine (LOB, JC, HRK), Farmington, Connecticut; Department of Statistics, University of Connecticut (OH, SD), Storrs, Connecticut; Department of Psychiatry, Division of Human Genetics in Psychiatry, Yale University School of Medicine (JG), VA Connecticut, West Haven, Connecticut; and Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina (RA), Charleston, South Carolina.
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  • Ofer Harel,

    1. From the Department of Psychiatry, Alcohol Research Center, University of Connecticut School of Medicine (LOB, JC, HRK), Farmington, Connecticut; Department of Statistics, University of Connecticut (OH, SD), Storrs, Connecticut; Department of Psychiatry, Division of Human Genetics in Psychiatry, Yale University School of Medicine (JG), VA Connecticut, West Haven, Connecticut; and Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina (RA), Charleston, South Carolina.
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  • Sourish Das,

    1. From the Department of Psychiatry, Alcohol Research Center, University of Connecticut School of Medicine (LOB, JC, HRK), Farmington, Connecticut; Department of Statistics, University of Connecticut (OH, SD), Storrs, Connecticut; Department of Psychiatry, Division of Human Genetics in Psychiatry, Yale University School of Medicine (JG), VA Connecticut, West Haven, Connecticut; and Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina (RA), Charleston, South Carolina.
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  • Joel Gelernter,

    1. From the Department of Psychiatry, Alcohol Research Center, University of Connecticut School of Medicine (LOB, JC, HRK), Farmington, Connecticut; Department of Statistics, University of Connecticut (OH, SD), Storrs, Connecticut; Department of Psychiatry, Division of Human Genetics in Psychiatry, Yale University School of Medicine (JG), VA Connecticut, West Haven, Connecticut; and Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina (RA), Charleston, South Carolina.
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  • Raymond Anton,

    1. From the Department of Psychiatry, Alcohol Research Center, University of Connecticut School of Medicine (LOB, JC, HRK), Farmington, Connecticut; Department of Statistics, University of Connecticut (OH, SD), Storrs, Connecticut; Department of Psychiatry, Division of Human Genetics in Psychiatry, Yale University School of Medicine (JG), VA Connecticut, West Haven, Connecticut; and Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina (RA), Charleston, South Carolina.
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  • Henry R. Kranzler

    1. From the Department of Psychiatry, Alcohol Research Center, University of Connecticut School of Medicine (LOB, JC, HRK), Farmington, Connecticut; Department of Statistics, University of Connecticut (OH, SD), Storrs, Connecticut; Department of Psychiatry, Division of Human Genetics in Psychiatry, Yale University School of Medicine (JG), VA Connecticut, West Haven, Connecticut; and Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina (RA), Charleston, South Carolina.
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Reprint requests: Henry R. Kranzler, MD, Department of Psychiatry, University of Connecticut School of Medicine, 263 Farmington Ave., Farmington, CT 06030-2103; Fax: 860-679-1316; E-mail: kranzler@psychiatry.uchc.edu

Abstract

Background:  Previous studies demonstrated, and replicated, an association between single nucleotide polymorphisms (SNPs) within the GABRA2 gene and risk for alcohol dependence. The present study examines the association of a GABRA2 SNP with another definition of alcohol involvement and with the effects of psychosocial treatment.

Methods:  European-American subjects (n = 812, 73.4% male) provided DNA samples for the analysis. All were participants in Project Matching Alcoholism Treatment to Client Heterogeneity (MATCH), a multi-center randomized clinical trial evaluating the efficacy of 3 types of psychosocial treatment for alcoholism: Cognitive Behavioral Therapy (CBT), Motivational Enhancement Therapy (MET), or twelve-step facilitation (TSF). The daily probabilities of drinking and heavy drinking were estimated during the 12-week treatment and 12-month post-treatment periods.

Results:  Subjects homozygous for the allele associated with low risk for alcohol dependence in previous studies had lower daily probabilities of drinking and heavy drinking in the present study. This low-risk allele was also associated with a greater difference in drinking outcomes between the treatments. In addition, it enhanced the relative superiority of TSF over CBT and MET. Population stratification was excluded as a confound using ancestry informative marker analysis.

Conclusions:  The assessment of genetic vulnerability may be relevant to studies of the efficacy of psychosocial treatment: GABRA2 genotype modifies the variance in drinking and can therefore moderate power for resolving differences between treatments.

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