Glucocorticoid Receptor (NR3C1) Gene Polymorphism Moderate Intervention Effects on the Developmental Trajectory of African-American Adolescent Alcohol Abuse

Yao Zheng, Dustin Albert, Robert J McMahon, Kenneth Dodge, Danielle Dick, Conduct Problems Prevention Research Group, Karen L Bierman, John D Coie, Kenneth A Dodge, Mark T Greenberg, John E Lochman, Robert J McMahon, Ellen E Pinderhughes, Yao Zheng, Dustin Albert, Robert J McMahon, Kenneth Dodge, Danielle Dick, Conduct Problems Prevention Research Group, Karen L Bierman, John D Coie, Kenneth A Dodge, Mark T Greenberg, John E Lochman, Robert J McMahon, Ellen E Pinderhughes

Abstract

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.

Keywords: Adolescent; Alcohol use; Developmental trajectory; Differential susceptibility; Genotype-environment interaction; Glucocorticoid receptor genes.

Figures

Figure 1
Figure 1
Proportion of past year alcohol abuse among African American adolescents from grade 7 (time 1) to 2 years post-high school (time 8) by carriage of the rs12655166 “C” allele and intervention status. The T/T group carried no copies of the C allele. The C Carriers group carried one or two copies of the C allele. Gene-by-intervention interaction effect was statistically significant (p < .001) for the linear slope of alcohol use over time.

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