Glucocorticoid Receptor (NR3C1) Gene Polymorphism Moderate Intervention Effects on the Developmental Trajectory of African-American Adolescent Alcohol Abuse.
- Authors
- Zheng, Yao; Albert, Dustin; McMahon, Robert J; Dodge, Kenneth; Dick, Danielle; Conduct Problems Prevention Research Group
- Year
- 2018
- Journal
- Prevention science : the official journal of the Society for Prevention Research
- PMID
- 27817096
- DOI
- 10.1007/s11121-016-0726-4
- PMCID
- PMC5420337
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.
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.
LLM interpretation
This figure consists of two line graphs showing the proportion of past year alcohol abuse over eight time points for African American adolescents, stratified by genotype (T/T and C Carriers) and group (Intervention vs. Control). In the T/T group, both intervention and control lines show a similar upward trend, ending between 0.25 and 0.30. In the C Carriers group, the control group shows a sharper increase in alcohol abuse over time compared to the intervention group, which plateaus around 0.20. The legend notes a statistically significant gene-by-intervention interaction effect (p < .001) for the linear slope of alcohol use.
| Name | Type |
|---|---|
| 5-HTTLPR | variant |
| 5-HTTLPR short allele variant local | variant |
| AA | cohort |
| academic performance | phenotype |
| adolescent alcohol use | phenotype |
| adolescent conduct problems | phenotype |
| adolescents | cohort |
| African American | cohort |
| aggression toward peers local | phenotype |
| alcohol | phenotype |
| alcohol abuse | phenotype |
| alcohol-related problems | phenotype |
| Alcohol Use | phenotype |
| antisocial personality disorder | phenotype |
| any past year alcohol abuse local | phenotype |
| behavioral disorders | phenotype |
| behavioral intervention local | drug |
| binge drinking | phenotype |
| Child antisocial behavior local | phenotype |
| childhood externalizing psychopathology local | phenotype |
| children | cohort |
| Classroom conduct problems local | phenotype |
| Cohort_1991_1993 local | cohort |
| conduct disorder | phenotype |
| control | cohort |
| control group | cohort |
| cortisol | drug |
| cortisol stress reactivity local | phenotype |
| disruptive and oppositional behavior local | phenotype |
| DRD2 | gene |
| DRD4 | gene |
| Driving under the influence | phenotype |
| drugs | drug |
| drunkenness | phenotype |
| Durham, NC local | cohort |
| EA | cohort |
| European ancestry | cohort |
| externalizing behavior | phenotype |
| externalizing disorders | phenotype |
| Externalizing problem score local | phenotype |
| Externalizing problems (Teacher’s Report Form of the CBCL) local | phenotype |
| family support | phenotype |
| Fast Track | cohort |
| Fast Track intervention | cohort |
| Fast Track trial local | cohort |
| general population | cohort |
| glucocorticoid resistance local | phenotype |
| grade 1 local | phenotype |
| grades 7–10 local | phenotype |
| Home behavior problems local | phenotype |
| HPA axis | anatomy |
| hypothalamus | anatomy |
| intervention | cohort |
| intervention families local | cohort |
| intervention group | cohort |
| intervention response | phenotype |
| intervention schools local | cohort |
| Nashville, TN local | cohort |
| Nr3c1 | gene |
| NR3C1 polymorphism local | variant |
| NR3C1 SNP | variant |
| other drug use | phenotype |
| parents | cohort |
| Past year alcohol abuse local | phenotype |
| peer substance use | phenotype |
| reduced HPA axis negative feedback local | phenotype |
| risky sexual behavior | phenotype |
| rs10482672 | variant |
| rs12655166 local | variant |
| rural PA local | cohort |
| Seattle, WA local | cohort |
| Severity-of-risk screen score local | phenotype |
| SLC6A3 | gene |
| SLC6A4 | gene |
| SNP | cohort |
| social-cognitive skill development local | phenotype |
| social-emotional competence local | phenotype |
| social rejection | phenotype |
| study cohort | cohort |
| substance abuse | phenotype |
| substance use | phenotype |
| suicide | phenotype |
| tobacco use | phenotype |
| young adults | cohort |
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In this knowledge base
| Title | Year | PMID |
|---|---|---|
| Commentary for Special Issue of Prevention Science "Using Genetics in Prevention: Science Fiction or Science Fact?". | 2018 | 28735446 |
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Comparing self-reported race and genetic ancestry for identifying potential differentially methylated sites in endometrial cancer: insights from African ancestry proportions using machine learning models. | Asif H et al. | — | 2025 | → |
| A systematic review of gene-by-intervention studies of alcohol and other substance use. | Neale ZE et al. | — | 2021 | → |
| Global and glucocorticoid receptor gene-specific (NR3C1) DNA methylation analysis in patients with cannabinoid or synthetic cannabinoid use disorder. | Pehlivan S et al. | — | 2021 | → |
| Polygenic Risk for Aggression Predicts Adult Substance Use Disorder Diagnoses via Substance Use Offending in Emerging Adulthood and is Moderated by a Family-Centered Intervention. | Elam KK et al. | — | 2021 | → |
| Metabolites and metabolic pathways associated with glucocorticoid resistance in pregnant African-American women. | Corwin E et al. | — | 2020 | → |
| Peer Alcohol Use Differentially Amplifies Genetic and Environmental Effects on Different Developmental Trajectories of Adolescent Alcohol Use. | Zheng Y et al. | — | 2019 | → |
| A systematic review: Candidate gene and environment interaction on alcohol use and misuse among adolescents and young adults. | Kim J et al. | — | 2018 | → |
| Commentary for Special Issue of Prevention Science "Using Genetics in Prevention: Science Fiction or Science Fact?" | Dick DM | — | 2018 | → |
| Genetic variations in genes of the stress response pathway are associated with prolonged abstinence from heroin. | Levran O et al. | — | 2018 | → |
| Genomics, Big Data, and Broad Consent: a New Ethics Frontier for Prevention Science. | Fisher CB et al. | — | 2018 | → |
| The Implications of Genetics for Prevention and Intervention Programming. | Musci RJ et al. | — | 2018 | → |
| Neuroendocrinology of a Male-Specific Pattern for Depression Linked to Alcohol Use Disorder and Suicidal Behavior. | Walther A et al. | — | 2016 | → |