Genes involved in stress response and alcohol use among high-risk African American youth

ABSTRACT

Background: Genetic and environmental factors influence substance use behaviors in youth. One of the known environmental risk factors is exposure to life stressors. The aim of this project is to study the interaction between NR3C1 and CRHBP, genes thought to be involved in stress pathways, exposure to stressful life events, and adolescent alcohol use/misuse. Methods: The sample included 541 African American individuals (ages 13–18) from the Genes, Environment, and Neighborhood Initiative, a subset of the Mobile Youth Survey sample from whom DNA and more extensive phenotypic data were collected. Participants were selected from high-poverty neighborhoods in Mobile, Alabama, with potential exposure to a variety of extreme life stressors. Results: A measure of stressful life events was significantly predictive of alcohol use/misuse. In addition, this association was significantly dependent upon the number of putative risk variants at rs1715749, a single-nucleotide polymorphism (SNP) in CRHBP (P ≤ .006). There was no significant interaction between NR3C1 and stressful life events with respect to alcohol use/misuse, after taking into account multiple testing. Conclusions: These findings suggest that CRHBP variants are potentially relevant for adolescent alcohol use/misuse among African American youth populations being reared within the context of stressful life events and warrant replication.

KEYWORDS:

• Adolescents
• alcohol
• stressful life events

Author contributions

B. Mustanski was responsible for the study concept and design. F. Aliev and J. E. Salvatore aided in performing the statistical analysis. J. E. Salvatore and D. M. Dick aided in drafting the manuscript. J. E. Salvatore and D. M. Dick shared senior authorship responsibilities for these analyses and the manuscript. All coauthors aided with the interpretation of the results and provided critical revision of the manuscript for important intellectual content. All authors reviewed the content and approved the final version for publication.

Funding

This project was supported by a grant from the National Institute on Drug Abuse (R01DA025039 to B.M.), from the National Institutes of Health's National Center for Advancing Translational Science (UL1TR000058), from grant K02AA018755 (to D.M.D.), and from grant F32AA022269 (to J.E.S). Funding provided to B.M. supported research conception and design and collection of data. N.G., J.E.S., and D.M.D. drafted the manuscript. Funding agencies supported data collection and individuals' effort on this work and were not involved with the development of the intellectual content of this publication.