Can Genetics Predict Response to Complex Behavioral Interventions? Evidence from a Genetic Analysis of the Fast Track Randomized Control Trial.
- Authors
- Albert, Dustin; Belsky, Daniel W; Crowley, D Max; Latendresse, Shawn J; Aliev, Fazil; Riley, Brien; Sun, Cuie; Conduct Problems Prevention Research Group; Dick, Danielle M; Dodge, Kenneth A
- Year
- 2015
- Journal
- Journal of policy analysis and management : [the journal of the Association for Public Policy Analysis and Management]
- PMID
- 26106668
- DOI
- 10.1002/pam.21811
- PMCID
- PMC4480598
Early interventions are a preferred method for addressing behavioral problems in high-risk children, but often have only modest effects. Identifying sources of variation in intervention effects can suggest means to improve efficiency. One potential source of such variation is the genome. We conducted a genetic analysis of the Fast Track randomized control trial, a 10-year-long intervention to prevent high-risk kindergarteners from developing adult externalizing problems including substance abuse and antisocial behavior. We tested whether variants of the glucocorticoid receptor gene NR3C1 were associated with differences in response to the Fast Track intervention. We found that in European-American children, a variant of NR3C1 identified by the single-nucleotide polymorphism rs10482672 was associated with increased risk for externalizing psychopathology in control group children and decreased risk for externalizing psychopathology in intervention group children. Variation in NR3C1 measured in this study was not associated with differential intervention response in African-American children. We discuss implications for efforts to prevent externalizing problems in high-risk children and for public policy in the genomic era.
Fast Track Randomized Controlled Trial Design.
Prevalence of Any Externalizing Psychopathology in European-American Fast Track Intervention and Control Children by Carriage of the rs10482672 “A” Allele.Notes:The G/G group carried no copies of the “A” allele. The “A” Carrier group carried one or two copies of the “A” allele.
Prevalence of Alcohol Abuse, Cannabis Abuse, Hard Drug Use, Attention Deficit/Hyperactivity Disorder, and Antisocial Personality Disorder in European-American Fast Track Intervention and Control Children by Carriage of the rs10482672 “A” Allele.Notes:The G/G group carried no copies of the “A” allele. The “A” Carrier group carried one or two copies of the “A” allele.
Delinquent Behavior, Problem Alcohol Use, and Cannabis Use in European-American Fast Track Control and Intervention Children by Carriage of the rs10482672 “A” Allele.Notes:The G/G group carried no copies of the “A” allele. The “A” Carrier group carried one or two copies of the “A” allele. Gene-by-intervention interaction effects were statistically significant (p<0.05) for mean levels of delinquency, alcohol use, and cannabis use and for change over time in alcohol and cannabis use. Details are reported in Appendix Table A5. (All appendices are available at the end of this article as it appears in JPAM online. Go to the publisher’s website and use the search engine to locate the article at: //ww3interscience.wiley.com/cgibin/jhome/34787.)
Pairwise Linkage Disequilibrium (R2) Between Candidate SNPs in NR3C1.Notes:Linkage disequilibrium plots were obtained from Haploview (Barrett et al., 2005). Values displayed in each box indicate the pairwise correlation (R2) between markers. Shading indicates the degree of correlation as measured by D', following the standard Haploview color scheme: high-confidence associations (LOD ≥ 2) are shaded from light pink to bright red based on the absolute value of D'; low-confidence associations (LOD < 2) are shaded white (D'<1) or blue (D'=1). Each subset of SNPs grouped within a black triangle is considered a “block” based on proximity and inter-correlation criteria defined by Gabriel et al. (2002). LOD is the log of the likelihood odds ratio, a measure of confidence in the value of D'.
| Name | Type |
|---|---|
| 1991 cohort local | cohort |
| 1992 cohort local | cohort |
| 1993 cohort local | cohort |
| 54 schools local | cohort |
| A local | variant |
| academic performance | phenotype |
| Accurate appraisal of benign social stimuli local | phenotype |
| ADHD | phenotype |
| adolescents | cohort |
| adrenal gland | anatomy |
| adverse childhood experiences | phenotype |
| adverse developmental outcomes local | phenotype |
| African American | cohort |
| African-American RCT participants local | cohort |
| African-Americans | cohort |
| aggression | phenotype |
| alcohol | phenotype |
| alcohol abuse | phenotype |
| Alcohol Use | phenotype |
| Alcohol Use Disorder | phenotype |
| antisocial personality disorder | phenotype |
| Any Externalizing Psychopathology local | phenotype |
| Any Externalizing Psychopathology indicator local | phenotype |
| attention deficit hyperactivity disorder | phenotype |
| behavioral disorders | phenotype |
| behavior problems | phenotype |
| better developmental outcomes local | phenotype |
| Biological sensitivity to stress local | phenotype |
| cannabis use | phenotype |
| CBCL Aggression local | phenotype |
| cocaine | phenotype |
| common variants | cohort |
| conduct disorder | phenotype |
| conduct-disordered children local | cohort |
| consortia | cohort |
| control | cohort |
| Control A carriers local | cohort |
| Control arm local | cohort |
| control children | cohort |
| control group | cohort |
| Control non-carriers local | cohort |
| cortisol | drug |
| crack | drug |
| decision making | phenotype |
| delinquency | phenotype |
| developmental outcomes | phenotype |
| deviant peers | phenotype |
| differential susceptibility | phenotype |
| drugs | drug |
| early-starting conduct problems local | phenotype |
| ecstasy | drug |
| educational attainment | phenotype |
| emotion regulation | phenotype |
| European-American subsample local | cohort |
| European population | cohort |
| externalizing behavior | phenotype |
| externalizing disorders | phenotype |
| Fast Track | cohort |
| Fast Track analytic sample local | cohort |
| Fast Track intervention | cohort |
| Fast Track intervention local | drug |
| Fast Track RCT local | cohort |
| Fast Track sample local | cohort |
| Fast Track treatment local | drug |
| Fast Track treatment group local | cohort |
| Full African-American sample local | cohort |
| Full Fast Track sample local | cohort |
| full sample | cohort |
| genetically at-risk children local | cohort |
| genetic differences | phenotype |
| genetic variants | cohort |
| genotype local | phenotype |
| heavy drinking | phenotype |
| high cortisol reactivity local | phenotype |
| high-risk children local | phenotype |
| high risk for persistent antisocial behavior local | phenotype |
| high-risk kindergarteners local | cohort |
| High-risk youth local | cohort |
| HPA axis | anatomy |
| Human capital interventions local | phenotype |
| hypothalamus | anatomy |
| inhalants | drug |
| intervention | cohort |
| intervention group | cohort |
| intervention response | phenotype |
| Kindergarten cohort local | cohort |
| Life skills local | phenotype |
| low cortisol reactivity local | phenotype |
| LSD | drug |
| marijuana | phenotype |
| marijuana abuse | phenotype |
| Middle school transition program local | cohort |
| mood disorders | phenotype |
| Mushrooms local | drug |
| Nr3c1 | gene |
| NR3C1 SNP | variant |
| NR3C1 variants local | variant |
| NRC31 local | gene |
| Parent monitoring local | phenotype |
| Parent-youth group intervention sessions local | cohort |
| PCP | drug |
| persistent antisocial behavior local | phenotype |
| persistent externalizing psychopathology local | phenotype |
| pituitary gland | anatomy |
| preschoolers local | cohort |
| preventive interventions local | drug |
| Randomized trials local | cohort |
| risk-behavior local | phenotype |
| rs10482672 | variant |
| rs10482672 A allele local | variant |
| rural African-Americans local | cohort |
| self-control | phenotype |
| Serious Substance Use local | phenotype |
| Severity-of-risk score local | phenotype |
| sex | phenotype |
| SNP | cohort |
| social cognition | phenotype |
| social rejection | phenotype |
| Social stress response local | phenotype |
| Speed local | drug |
| stress | phenotype |
| stress physiology local | phenotype |
| stress response | phenotype |
| Strong African American Families intervention local | cohort |
| substance abuse | phenotype |
| substance use | phenotype |
| Summer employment local | phenotype |
| temperamental characteristics local | phenotype |
| Threat appraisal of benign social stimuli local | phenotype |
| tobacco use | phenotype |
| TOCA-R Authority Acceptance score local | phenotype |
| treated children local | cohort |
| Treated non-carriers local | cohort |
| treatment group | cohort |
| Unprescribed pills local | drug |
| violence | phenotype |
| Vocational opportunities local | phenotype |
| White children | cohort |
| Youth Forums local | cohort |
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| Post-GWAS in Psychiatric Genetics: A Developmental Perspective on the "Other" Next Steps. | Dick DM et al. | — | 2018 | → |
| Vantage sensitivity: a framework for individual differences in response to psychological intervention. | de Villiers B et al. | — | 2018 | → |
| New Clinically Relevant Findings about Violence by People with Schizophrenia. | Hodgins S et al. | — | 2017 | → |
| Vantage Sensitivity: Environmental Sensitivity to Positive Experiences as a Function of Genetic Differences. | Pluess M | — | 2017 | → |
| Differential susceptibility to environmental influences: Interactions between child temperament and parenting in adolescent alcohol use. | Rioux C et al. | — | 2016 | → |
| Genetic influences on adolescent behavior. | Dick DM et al. | — | 2016 | → |
| Developmental mediation of genetic variation in response to the Fast Track prevention program. | Albert D et al. | — | 2015 | → |
| The hidden efficacy of interventions: gene×environment experiments from a differential susceptibility perspective. | Bakermans-Kranenburg MJ et al. | — | 2015 | → |