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Gender-Specific Gene–Environment Interaction in Alcohol Dependence: The Impact of Daily Life Events and GABRA2

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Abstract

Gender-moderated gene–environment interactions are rarely explored, raising concerns about inaccurate specification of etiological models and inferential errors. The current study examined the influence of gender, negative and positive daily life events, and GABRA2 genotype (SNP rs279871) on alcohol dependence, testing two- and three-way interactions between these variables using multi-level regression models fit to data from 2,281 White participants in the Collaborative Study on the Genetics of Alcoholism. Significant direct effects of variables of interest were identified, as well as gender-specific moderation of genetic risk on this SNP by social experiences. Higher levels of positive life events were protective for men with the high-risk genotype, but not among men with the low-risk genotype or women, regardless of genotype. Our findings support the disinhibition theory of alcohol dependence, suggesting that gender differences in social norms, constraints and opportunities, and behavioral undercontrol may explain men and women’s distinct patterns of association.

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Acknowledgment

This research was funded in part by a grant from the Peter F. McManus Charitable Trust. The Collaborative Study on the Genetics of Alcoholism (COGA), Principal Investigators B. Porjesz, V. Hesselbrock, H. Edenberg, L. Bierut, includes ten different centers: University of Connecticut (V. Hesselbrock); Indiana University (H.J. Edenberg, J. Nurnberger Jr., T. Foroud); University of Iowa (S. Kuperman, J. Kramer); SUNY Downstate (B. Porjesz); Washington University in St. Louis (L. Bierut, A. Goate, J. Rice, K. Bucholz); University of California at San Diego (M. Schuckit); Rutgers University (J. Tischfield); Southwest Foundation (L. Almasy), Howard University (R. Taylor) and Virginia Commonwealth University (D. Dick). A. Parsian and M. Reilly are the NIAAA Staff Collaborators. This national collaborative study is supported by NIH Grant U10 AA008401 from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the National Institute on Drug Abuse (NIDA). Funding support for GWAS genotyping, which was performed at the Johns Hopkins University Center for Inherited Disease Research, was provided by the National Institute on Alcohol Abuse and Alcoholism, the NIH GEI (U01HG004438), and the NIH contract “High throughput genotyping for studying the genetic contributions to human disease” (HHSN268200782096C). The authors thank Kim Doheny and Elizabeth Pugh from CIDR and Justin Paschall from the NCBI dbGaP staff for valuable assistance with genotyping and quality control in developing the dataset available at dbGaP.

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Authors and Affiliations

  1. Department of Sociology, University of Kentucky, 1515 Patterson Office Tower, Lexington, KY, 40506-0027, USA

    Brea L. Perry

  2. Department of Sociology, Indiana University, Bloomington, IN, USA

    Bernice A. Pescosolido

  3. Department of Psychiatry, Washington University in St. Louis, St. Louis, MO, USA

    Kathleen Bucholz

  4. Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA

    Howard Edenberg & John I. Nurnberger Jr.

  5. Department of Psychiatry, University of Iowa College of Medicine, Iowa City, IA, USA

    John Kramer & Samuel Kuperman

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

    Marc Alan Schuckit

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  1. Brea L. Perry
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Perry, B.L., Pescosolido, B.A., Bucholz, K. et al. Gender-Specific Gene–Environment Interaction in Alcohol Dependence: The Impact of Daily Life Events and GABRA2. Behav Genet 43, 402–414 (2013). https://doi.org/10.1007/s10519-013-9607-9

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