Glucocorticoid Receptor (NR3C1) Gene Polymorphism Moderate Intervention Effects on the Developmental Trajectory of African-American Adolescent Alcohol Abuse
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Accumulative evidence from recent genotype × intervention studies suggests that individuals carrying susceptible genotypes benefit more from intervention and provides one avenue to identify subgroups that respond differentially to intervention. This study examined the moderation by glucocorticoid receptor (NR3C1) gene variants of intervention effects on the developmental trajectories of alcohol abuse through adolescence. Participants were randomized into Fast Track intervention and control groups self-reported past-year alcohol abuse annually from grade 7 through 2 years post-high school and provided genotype data at age 21 (69% males; European Americans [EAs] = 270, African-Americans [AAs] = 282). Latent growth curve models were fit to examine developmental trajectories of alcohol abuse. The interactions of 10 single nucleotide polymorphisms (SNPs) in NR3C1 with intervention were examined separately. Both EAs and AAs showed significant increases in past-year alcohol abuse with substantial inter-individual differences in rates of linear growth. AAs showed lower general levels and slower rates of linear growth than EAs. Adjusting for multiple tests, one NR3C1 SNP (rs12655166) significantly moderated intervention effects on the developmental trajectories of alcohol abuse among AAs. Intervention effects on the rates of linear growth were stronger among AAs carrying minor alleles than those not carrying minor alleles. The findings highlight the importance of taking a developmental perspective on adolescent alcohol use and have implications for future intervention design and evaluation by identifying subgroups that could disproportionally benefit from intervention.
KeywordsDifferential susceptibility Glucocorticoid receptor genes Alcohol use Adolescent Developmental trajectory Genotype-environment interaction
This work used data from Fast Track project (for additional information concerning Fast Track, see http://www.fasttrackproject.org). We are grateful for the collaboration of the Durham Public Schools, the Metropolitan Nashville Public Schools, the Bellefonte Area Schools, the Tyrone Area Schools, the Mifflin County Schools, the Highline Public Schools, and the Seattle Public Schools. We appreciate the hard work and dedication of the many staff members who implemented the project, collected the evaluation data, and assisted with data management and analyses.
The Conduct Problems Prevention Research Group
Karen L. Bierman, Pennsylvania State University; John D. Coie, Duke University; Kenneth A. Dodge, Duke University; Mark T. Greenberg, Pennsylvania State University; John E. Lochman, University of Alabama; Robert J. McMahon, Simon Fraser University and BC Children’s Hospital; and Ellen E. Pinderhughes, Tufts University.
Compliance with Ethical Standards
This work was supported by National Institute of Mental Health (NIMH) Grants R18 MH48043, R18 MH50951, R18 MH50952, R18 MH50953, K05MH00797, and K05MH01027; National Institute on Drug Abuse (NIDA) Grants DA016903, K05DA15226, and P30DA023026; and Department of Education Grant S184U30002. The Center for Substance Abuse Prevention also provided support through a memorandum of agreement with the NIMH. Additional support for the preparation of this work was provided by a LEEF B.C. Leadership Chair award, Child & Family Research Institute Investigator Salary and Investigator Establishment Awards, and a Canada Foundation for Innovation award to Robert J. McMahon.
Conflict of Interest
Drs. Bierman, Coie, Dodge, Greenberg, Lochman, McMahon, and Pinderhughes are the principal investigators on the Fast Track Project and have a publishing agreement with Guilford Publications, Inc. Royalties from that agreement will be donated to a professional organization. They are also authors of the PATHS curriculum and donate all royalties from Channing-Bete, Inc. to a professional organization. Dr. Greenberg is a developer of the PATHS curriculum and has a separate royalty agreement with Channing-Bete, Inc. Bierman, Coie, Dodge, Greenberg, Lochman, and McMahon are the developers of the Fast Track curriculum and have publishing and royalty agreements with Guilford Publications, Inc. Dr. McMahon is a coauthor of Helping the Noncompliant Child and has a royalty agreement with Guilford Publications, Inc.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
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