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Examination of Genetic Variation in GABRA2 with Conduct Disorder and Alcohol Abuse and Dependence in a Longitudinal Study

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Abstract

Previous studies have shown associations between single nucleotide polymorphisms (SNPs) in gamma aminobutyric acid receptor alpha 2 (GABRA2) and adolescent conduct disorder (CD) and alcohol dependence in adulthood, but not adolescent alcohol dependence. The present study was intended as a replication and extension of this work, focusing on adolescent CD, adolescent alcohol abuse and dependence (AAD), and adult AAD. Family based association tests were run using Hispanics and non-Hispanic European American subjects from two independent longitudinal samples. Although the analysis provided nominal support for an association with rs9291283 and AAD in adulthood and CD in adolescence, the current study failed to replicate previous associations between two well replicated GABRA2 SNPs and CD and alcohol dependence. Overall, these results emphasize the utility of including an independent replication sample in the study design, so that the results from an individual sample can be weighted in the context of its reproducibility.

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Acknowledgments

Thanks to Thomas Crowley, an important contributor to the CADD and GADD data collection. This work supported by grants from the National Institutes of Health: AA017889, AA019447, DA011015, DA012845, and DA017637.

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all patients for being included in the study.

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Authors and Affiliations

  1. Institute for Behavioral Genetics, University of Colorado, Boulder, CO, USA

    Whitney E. Melroy, Matthew B. McQueen, Robin P. Corley, Michael C. Stallings, John K. Hewitt & Marissa A. Ehringer

  2. School of Medicine, University of Maryland, Baltimore, MD, USA

    Sarah H. Stephens

  3. Department of Psychiatry, University of Colorado Anschutz Medical Campus, Aurora, CO, USA

    Joseph T. Sakai

  4. Department of Biobehavioral Health, Pennsylvania State University, University Park, PA, USA

    Helen M. Kamens

  5. MCDB, University of Colorado, Boulder, CO, USA

    Kenneth S. Krauter

  6. Department of Psychology and Psychiatry, University of California, San Diego, CA, USA

    Sandra A. Brown

  7. Department of Integrative Physiology, Institute for Behavioral Genetics, University of Colorado, 447 UCB, Boulder, CO, 80309-0447, USA

    Marissa A. Ehringer

  8. Department of Psychiatry, University of Colorado School of Medicine, Aurora, CO, USA

    Christian J. Hopfer

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  1. Whitney E. Melroy
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Correspondence to Marissa A. Ehringer.

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Melroy, W.E., Stephens, S.H., Sakai, J.T. et al. Examination of Genetic Variation in GABRA2 with Conduct Disorder and Alcohol Abuse and Dependence in a Longitudinal Study. Behav Genet 44, 356–367 (2014). https://doi.org/10.1007/s10519-014-9653-y

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