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.

Published on Jun 11, 2021in Behavior Genetics2.231
· DOI :10.1007/S10519-021-10070-Y
Kit K. Elam13
Estimated H-index: 13
(IU: Indiana University),
Chung Jung Mun9
Estimated H-index: 9
(Johns Hopkins University)
+ 1 AuthorsThao Ha16
Estimated H-index: 16
(ASU: Arizona State University)
Sources
Abstract
A substance use offense reflects an encounter with law enforcement and the court system in response to breaking the law which may increase risk for substance use problems later in life. Individuals may also be at risk for substance use offending and substance use problems based on genetic predisposition. We examined a mediation model in which polygenic risk for aggression predicted adult substance use disorder diagnoses (SUD) via substance use offending in emerging adulthood. In addition, we explored for potential attenuation of genetic influences on these outcomes by a family-based intervention, the Family Check-Up (FCU). Secondary data analyses based upon the Project Alliance 1 sample was conducted among those with genetic data (n = 631; 322 from control and 309 from FCU intervention). The sample was ethnically diverse (30% African American, 44% European American, 6% Latinx, 4% Asian American, 3% Native American, and 13% Other). Greater polygenic risk for aggression was found to increase risk for substance use violations (age 19-23), which in turn was associated with greater likelihood of being diagnosed with SUD at age 27. A gene-by-intervention effect was found in which individuals in the control group had greater risk for SUD with increasing polygenic risk for aggression. Some convergence in results was found when replicating analyses in African American and European American subgroups. Results imply that genetic predisposition may increase risk for problematic substance use later in life via antisocial behavior, such as substance use offending, and that this can be attenuated by a family-centered intervention.
📖 Papers frequently viewed together
5 Citations
3 Citations
2020
References62
Newest
#1Guiyan Ni (UQ: University of Queensland)H-Index: 5
#2Jian Zeng (UQ: University of Queensland)H-Index: 16
Last. Naomi R. Wray (UQ: University of Queensland)H-Index: 102
view all 14 authors...
Abstract Background Polygenic scores (PGSs), which assess the genetic risk of individuals for a disease, are calculated as a weighted count of risk alleles identified in genome-wide association studies (GWASs). PGS methods differ in which DNA variants are included and the weights assigned to them; some require an independent tuning sample to help inform these choices. PGSs are evaluated in independent target cohorts with known disease status. Variability between target cohorts is observed in app...
3 CitationsSource
#1C.A. HartmanH-Index: 8
Last. Ilja M. NolteH-Index: 1
view all 5 authors...
1 CitationsSource
#1Kit K. Elam (IU: Indiana University)H-Index: 13
#1Kit K. Elam (IU: Indiana University)H-Index: 2
Last. Kathryn Lemery-Chalfant (ASU: Arizona State University)H-Index: 28
view all 6 authors...
Aggressive behavior in middle childhood can contribute to peer rejection, subsequently increasing risk for substance use in adolescence. However, the quality of peer relationships a child experiences can be associated with his or her genetic predisposition, a genotype-environment correlation (rGE). In addition, recent evidence indicates that psychosocial preventive interventions can buffer genetic predispositions for negative behavior. The current study examined associations between polygenic ri...
2 CitationsSource
#1Peter B. Barr (VCU: Virginia Commonwealth University)H-Index: 10
#2Jessica E. Salvatore (VCU: Virginia Commonwealth University)H-Index: 19
Last. Danielle M. Dick (VCU: Virginia Commonwealth University)H-Index: 87
view all 12 authors...
Shared genetic factors contribute to the high degree of comorbidity among externalizing problems (e.g. substance use and antisocial behavior). We leverage this common genetic etiology to identify genetic influences externalizing problems in participants from the Collaborative Study on the Genetics of Alcoholism (European ancestry = 7568; African ancestry = 3274). We performed a family-based genome-wide association study (GWAS) on externalizing scores derived from criterion counts of five DSM dis...
4 CitationsSource
#1Stephanie Zellers (UMN: University of Minnesota)H-Index: 5
#2Robin P. Corley (CU: University of Colorado Boulder)H-Index: 72
Last. Scott I. Vrieze (UMN: University of Minnesota)H-Index: 25
view all 10 authors...
Externalizing psychopathology in early adolescence is a highly heritable risk factor for drug use, yet how it relates to marijuana use development is not well-characterized. We evaluate this issue in independent twin samples from Colorado (N = 2608) and Minnesota (N = 3630), assessed from adolescence to early adulthood. We used a biometric latent growth model of marijuana use frequency with data from up to five waves of assessment from ages 14 to 30, to examine change in marijuana use and its re...
3 CitationsSource
#1Yanli Zhang-James (State University of New York Upstate Medical University)H-Index: 17
Last. Stephen V. Faraone (University of Bergen)H-Index: 213
view all 7 authors...
Human genome-wide association studies (GWAS), transcriptome analyses of animal models, and candidate gene studies have advanced our understanding of the genetic architecture of aggressive behaviors. However, each of these methods presents unique limitations. To generate a more confident and comprehensive view of the complex genetics underlying aggression, we undertook an integrated, cross-species approach. We focused on human and rodent models to derive eight gene lists from three main categorie...
29 CitationsSource
#1Cortney Simmons (UCI: University of California, Irvine)H-Index: 5
#2Zachary Rowan (SFU: Simon Fraser University)H-Index: 5
Last. Elizabeth Cauffman (UCI: University of California, Irvine)H-Index: 64
view all 6 authors...
Abstract Life history theory has been used to understand how harsh and unpredictable environments contribute to risk behaviors. The theory suggests that exposure to negative environments leads individuals to adopt a “fast” life strategy, which is hypothesized to make individuals more likely to engage in risky behavior that is associated with immediate rewards. Using data from a sample of 1216 justice-involved male youth, we defined distinct groups of youth with a “fast” versus “slow” life strate...
3 CitationsSource
#1Sally I.Chun Kuo (VCU: Virginia Commonwealth University)H-Index: 13
#2Jessica E. Salvatore (VCU: Virginia Commonwealth University)H-Index: 19
Last. Danielle M. Dick (VCU: Virginia Commonwealth University)H-Index: 87
view all 6 authors...
Alcohol problems are influenced by both genetic and environmental factors. Evidence from twin models and measured gene-environment interaction studies has demonstrated that the importance of genetic influences changes as a function of the environment. Research has also shown that family-centered interventions may protect genetically susceptible youth from developing substance use problems. In this study, we brought large-scale gene identification findings into an intervention study to examine ge...
5 CitationsSource
#1Kit K. Elam (IU: Indiana University)H-Index: 13
#1Kit K. ElamH-Index: 2
Last. Kathryn Lemery-Chalfant (ASU: Arizona State University)H-Index: 28
view all 5 authors...
Previous approaches for creating polygenic risk scores (PRSs) do not explicitly consider the biological or developmental relevance of the genetic variants selected for inclusion. We applied gene set enrichment analysis to meta-GWAS data to create developmentally targeted, functionally informed PRSs. Using two developmentally matched meta-GWAS discovery samples, separate PRSs were formed, then examined in time-varying effect models of aggression in a second, longitudinal sample of children (n = 5...
7 CitationsSource
#1Kit K. Elam (ASU: Arizona State University)H-Index: 13
#2Laurie Chassin (ASU: Arizona State University)H-Index: 84
Last. Danielle Pandika (ASU: Arizona State University)H-Index: 5
view all 3 authors...
Poor family cohesion and elevated adolescent aggression are associated with greater alcohol use in adolescence and early adulthood. In addition, evocative gene–environment correlations ( r GEs) can underlie the interplay between offspring characteristics and negative family functioning, contributing to substance use. Gene–environment interplay has rarely been examined in racial/ethnic minority populations. The current study examined adolescents’ polygenic risk scores for aggression in evocative ...
14 CitationsSource
Cited By1
Newest
#1Kit K. Elam (IU: Indiana University)H-Index: 13
#2Lisabeth F. DiLalla (Southern Illinois University School of Medicine)H-Index: 24
Source