Interplay between genetic risk and the parent environment in adolescence and substance use in young adulthood: A TRAILS study

Abstract Many adolescents start using tobacco, alcohol, and cannabis. Genetic vulnerability, parent characteristics in young adolescence, and interaction (GxE) and correlation (rGE) between these factors could contribute to the development of substance use. Using prospective data from the TRacking Adolescent Individuals’ Lives Survey (TRAILS; N = 1,645), we model latent parent characteristics in young adolescence to predict young adult substance use. Polygenic scores (PGS) are created based on genome-wide association studies (GWAS) for smoking, alcohol use, and cannabis use. Using structural equation modeling we model the direct, GxE, and rGE effects of parent factors and PGS on young adult smoking, alcohol use, and cannabis initiation. The PGS, parental involvement, parental substance use, and parent–child relationship quality predicted smoking. There was GxE such that the PGS amplified the effect of parental substance use on smoking. There was rGE between all parent factors and the smoking PGS. Alcohol use was not predicted by genetic or parent factors, nor by interplay. Cannabis initiation was predicted by the PGS and parental substance use, but there was no GxE or rGE. Genetic risk and parent factors are important predictors of substance use and show GxE and rGE in smoking. These findings can act as a starting point for identifying people at risk.

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Chromatin architecture in addiction circuitry elucidates biological mechanisms underlying cigarette smoking and alcohol use traits.

10.1101/2021.03.18.436046 ◽

2021 ◽

Author(s):

Nancy Y.A Sey ◽

Benxia Hu ◽

Marina Iskhakova ◽

Huaigu Sun ◽

Neda Shokrian ◽

...

Keyword(s):

Risk Factors ◽

Alcohol Use ◽

Cigarette Smoking ◽

Genetic Risk ◽

Target Genes ◽

Association Studies ◽

Critical Role ◽

Genetic Risk Factors ◽

Genome Wide Association Studies ◽

Risk Genes

Cigarette smoking and alcohol use are among the most prevalent substances used worldwide and account for a substantial proportion of preventable morbidity and mortality, underscoring the public health significance of understanding their etiology. Genome-wide association studies (GWAS) have successfully identified genetic variants associated with cigarette smoking and alcohol use traits. However, the vast majority of risk variants reside in non-coding regions of the genome, and their target genes and neurobiological mechanisms are unknown. Chromosomal conformation mappings can address this knowledge gap by charting the interaction profiles of risk-associated regulatory variants with target genes. To investigate the functional impact of common variants associated with cigarette smoking and alcohol use traits, we applied Hi-C coupled MAGMA (H-MAGMA) built upon cortical and midbrain dopaminergic neuronal Hi-C datasets to GWAS summary statistics of nicotine dependence, cigarettes per day, problematic alcohol use, and drinks per week. The identified risk genes mapped to key pathways associated with cigarette smoking and alcohol use traits, including drug metabolic processes and neuronal apoptosis. Risk genes were highly expressed in cortical glutamatergic, midbrain dopaminergic, GABAergic, and serotonergic neurons, suggesting them as relevant cell types in understanding the mechanisms by which genetic risk factors influence cigarette smoking and alcohol use. Lastly, we identified pleiotropic genes between cigarette smoking and alcohol use traits under the assumption that they may reveal substance-agnostic, shared neurobiological mechanisms of addiction. The number of pleiotropic genes was ~26-fold higher in dopaminergic neurons than in cortical neurons, emphasizing the critical role of ascending dopaminergic pathways in mediating general addiction phenotypes. Collectively, brain region- and neuronal subtype-specific 3D genome architecture refines neurobiological hypotheses for smoking, alcohol, and general addiction phenotypes by linking genetic risk factors to their target genes.

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The Effect of Home Environment on Adolescent Substance Use and Depressive Symptoms

Journal of Drug Issues ◽

10.1177/002204269702700412 ◽

1997 ◽

Vol 27 (4) ◽

pp. 851-877 ◽

Cited By ~ 30

Author(s):

S. Susan Su ◽

John P. Hoffmann ◽

Dean R. Gerstein ◽

Robert A. Johnson

Keyword(s):

Substance Use ◽

Depressive Symptoms ◽

Affective Disorder ◽

Substance Use Disorder ◽

Structural Equation ◽

Panel Study ◽

Adolescent Substance Use ◽

Equation Modeling ◽

Adolescent Substance ◽

Parental Substance Use

We used data from the screening phase and first two waves of a panel study to compare the home environments of families with a substance-abusing parent, families with a depressed parent, and families in a comparison group. We diagnosed substance use disorder and affective disorder by administering the Structural Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders (third edition, revised) to each participating parent. The data suggest that families in which parents display a substance use disorder are very similar to those in which parents suffer from affective disorder, in terms of negative life events and lower family cohesion. The results of structural equation modeling indicate that parental substance use disorder and parental affective disorder influence adolescent substance use and depressive symptoms. In addition, parental substance use disorder has a direct influence on adolescent substance use at the time the first-wave data were collected, but this effect does not persist over time.

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Motives for Alcohol and Marijuana Use as Predictors of Use and Problem Use Among Young Adult College Students

Journal of Drug Issues ◽

10.1177/0022042620917101 ◽

2020 ◽

Vol 50 (4) ◽

pp. 359-377

Author(s):

Akilah Patterson ◽

Milkie Vu ◽

Regine Haardörfer ◽

Michael Windle ◽

Carla J. Berg

Keyword(s):

College Students ◽

Substance Use ◽

Young Adult ◽

Alcohol Use ◽

Problem Drinking ◽

Marijuana Use ◽

Problem Alcohol Use ◽

And Coping ◽

Alcohol Users ◽

Problem Alcohol

This study examined (a) differences between alcohol-only users and alcohol–marijuana co-users and (b) motives for use in relation to alcohol and marijuana use and problem use. Spring 2016 data among 1,870 past 4-month alcohol users (63.6% female, 69.1% White) from seven Georgia colleges/universities were analyzed cross-sectionally and with regard to problem use measured 4 months later. Correlates of co-use ( n = 345; vs. alcohol-only use, n = 1,525) included greater alcohol and marijuana use frequency, problem drinking and marijuana use, and alcohol use motives ( p’s < .05). Controlling for covariates, alcohol use frequency correlated with greater marijuana use frequency and Coping and Self-enhancement alcohol use motives, but lower Conformity alcohol use motives ( p’s < .001); greater Coping and Self-enhancement alcohol use motives ( p’s < .01) predicted problem alcohol use. Marijuana use frequency correlated with greater Coping and Expansion marijuana use motives ( p’s < .05); greater Expansion marijuana use motives ( p = .005) predicted problem marijuana use. College-based substance use interventions should target Coping and Self-enhancement alcohol use motives and Expansion marijuana use motives.

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Meta-analysis of problematic alcohol use in 435,563 individuals identifies 29 risk variants and yields insights into biology, pleiotropy and causality

10.1101/738088 ◽

2019 ◽

Cited By ~ 5

Author(s):

Hang Zhou ◽

Julia M. Sealock ◽

Sandra Sanchez-Roige ◽

Toni-Kim Clarke ◽

Daniel Levey ◽

...

Keyword(s):

Substance Use ◽

Alcohol Use ◽

Genetic Relationships ◽

Meta Analysis ◽

European Ancestry ◽

Polygenic Risk Score ◽

Genome Wide Association Studies ◽

Problematic Alcohol ◽

Risk Variants ◽

Problematic Alcohol Use

AbstractProblematic alcohol use (PAU) is a leading cause of death and disability worldwide. Although genome-wide association studies (GWASs) have identified PAU risk genes, the genetic architecture of this trait is not fully understood. We conducted a proxy-phenotype meta-analysis of PAU combining alcohol use disorder and problematic drinking in 435,563 European-ancestry individuals. We identified 29 independent risk variants, 19 of them novel. PAU was genetically correlated with 138 phenotypes, including substance use and psychiatric traits. Phenome-wide polygenic risk score analysis in an independent biobank sample (BioVU, n=67,589) confirmed the genetic correlations between PAU and substance use and psychiatric disorders. Genetic heritability of PAU was enriched in brain and in genomic conserved and regulatory regions. Mendelian randomization suggested causal effects on liability to PAU of substance use, psychiatric status, risk-taking behavior, and cognitive performance. In summary, this large PAU meta-analysis identified novel risk loci and revealed genetic relationships with numerous other outcomes.

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Interest in Genetic Feedback for Alcohol Use Disorder and Related Substance Use and Psychiatric Outcomes among Young Adults

Brain Sciences ◽

10.3390/brainsci10121007 ◽

2020 ◽

Vol 10 (12) ◽

pp. 1007

Author(s):

Morgan Driver ◽

Sally Kuo ◽

Danielle Dick ◽

Keyword(s):

Substance Use ◽

Alcohol Use ◽

Genetic Risk ◽

Alcohol Use Disorder ◽

Genetic Risk Score ◽

Related Substance ◽

Direct To Consumer ◽

Sizable Proportion ◽

Psychiatric Outcomes ◽

The Individual

An exponential growing number of individuals are accessing genetic risk information via direct to consumer companies. Alcohol dependence is the third most accessed genetic risk score on a publicly available direct to consumer website. Better understanding of the degree to which individuals are interested in receiving personalized genetic feedback, the factors that relate to interest, and genetic knowledge will be critical to lay the foundation for precision medicine initiatives, especially for substance use and psychiatric outcomes, where less is known. To assess interest in receiving genetic feedback for alcohol use disorder (AUD) and understanding of genetic concepts related to psychiatric conditions, we conducted a survey with participants recruited from a registry that enrolled incoming cohorts of freshmen at an urban public university; 205 participants (76.5% female; 58.9% self-reported as White; Mage = 24.48 years) completed the survey. Results indicated that participants are highly interested in receiving genetic feedback for AUD (79.0%) but there is a lack of understanding of complex genetic concepts in a sizable proportion of the sample (25.4%). Additional research is needed to assess how to address this lack of knowledge before genetic feedback for AUD can be returned in a way that benefits the individual.

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Shared genetic risk between eating disorder‐ and substance‐use‐related phenotypes: Evidence from genome‐wide association studies

Addiction Biology ◽

10.1111/adb.12880 ◽

2020 ◽

Vol 26 (1) ◽

Cited By ~ 3

Author(s):

Melissa A. Munn‐Chernoff ◽

Emma C. Johnson ◽

Yi‐Ling Chou ◽

Jonathan R.I. Coleman ◽

Laura M. Thornton ◽

...

Keyword(s):

Substance Use ◽

Eating Disorder ◽

Genetic Risk ◽

Association Studies ◽

Genome Wide Association ◽

Genome Wide Association Studies ◽

Genome Wide ◽

Shared Genetic

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The relation of adolescent substance use to young adult autonomy, positive activity involvement, and perceived competence

Development and Psychopathology ◽

10.1017/s0954579499002382 ◽

1999 ◽

Vol 11 (4) ◽

pp. 915-932 ◽

Cited By ~ 45

Author(s):

LAURIE CHASSIN ◽

STEVEN C. PITTS ◽

CHRISTIAN DELUCIA

Keyword(s):

Substance Use ◽

Young Adult ◽

Alcohol Use ◽

Drug Use ◽

Young Adulthood ◽

Heavy Drinking ◽

Perceived Competence ◽

Adolescent Substance Use ◽

Adolescent Substance ◽

Activity Involvement

The current paper uses data from a longitudinal study of a high-risk sample to test the relation between adolescent alcohol and drug use and later young adult autonomy, positive activity involvement, and perceived competence. Participants (children of alcoholics and demographically matched controls) were assessed in three annual interviews in adolescence (mean age: 12.7 years at Time 1) and then again 5–7 years later, in young adulthood (median age: 20 years). Path analyses and latent growth curve models tested the effects of adolescent substance use on both self-reported and collateral-reported outcomes, controlling for correlated risk factors (parental alcoholism, adolescent psychopathology, and parental support), preexisting levels of the outcome, and concurrent young adult substance use. Results showed that adolescent drug use had a significant, unique negative effect on later autonomy and perceived competence. Alcohol use effects were more complex. Adolescent heavy drinking was associated with less positive adult outcomes, but more so in collateral reports than in self-reported outcomes. Moreover, young adult heavy drinking was either uncorrelated with or positively correlated with higher levels of perceived competence, suggesting different developmental significance of alcohol use in adolescence than in young adulthood.

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The Deterrence Hypothesis Reexamined: Sports Participation and Substance Use among Young Adults

Journal of Drug Issues ◽

10.1177/002204260303300108 ◽

2003 ◽

Vol 33 (1) ◽

pp. 193-221 ◽

Cited By ~ 36

Author(s):

David Eitle ◽

R. Jay Turner ◽

Tamela McNulty Eitle

Keyword(s):

High School ◽

Substance Use ◽

Young Adult ◽

Alcohol Use ◽

Drug Use ◽

Protective Factor ◽

Sports Participation ◽

High School Sports ◽

School Sports ◽

Deterrence Hypothesis

The widely held notion that sports participation reduces subsequent risk of substance use is evaluated with longitudinal data of a representative sample of youth when they were in their preteen and young adult years. Unlike previous inquiries into the deterrence hypothesis, the present study controls for other major factors previously found to be predictive of alcohol and drug use. Results of analyses revealed that contrary to the deterrence hypothesis, playing high school sports does not appear to be a protective factor that lowers one's involvement in young adult alcohol or drug use – with one exception. Subgroup analyses revealed that among blacks, the greater the extent of high school sports participation the less the risk of substance use. In direct contradiction to the deterrence hypothesis, playing high school sports was found to be positively associated with alcohol use for whites, even in the context of other major predictors of alcohol use. Further analyses revealed that the positive association between sports participation and alcohol use appeared to exist only for white males. The implications of these results are discussed.

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Investigating causal pathways between liability to ADHD and substance use, and liability to substance use and ADHD risk, using Mendelian randomization

10.1101/524769 ◽

2019 ◽

Cited By ~ 1

Author(s):

Jorien L Treur ◽

Ditte Demontis ◽

George Davey Smith ◽

Hannah Sallis ◽

Tom G Richardson ◽

...

Keyword(s):

Substance Use ◽

Alcohol Use ◽

Genetic Variants ◽

Mendelian Randomization ◽

Smoking Initiation ◽

Cannabis Use ◽

Causal Effects ◽

Sensitivity Analyses ◽

Genome Wide Association Studies ◽

Causal Pathways

ABSTRACTBackgroundAttention-deficit hyperactivity disorder (ADHD) has consistently been associated with substance (ab)use, but the nature of this association is not fully understood. In view of preventive efforts, a vital question is whether there are causal effects, from ADHD to substance use and/or from substance use to ADHD.MethodsWe applied bidirectional Mendelian randomization using summary-level data from the largest available genome-wide association studies (GWASs) on ADHD, smoking (initiation, cigarettes/day, cessation, and a compound measure of lifetime smoking), alcohol use (drinks/week and alcohol use disorder), cannabis use (initiation and cannabis use disorder (CUD)) and coffee consumption (cups/day). Genetic variants robustly associated with the ‘exposure’ were selected as instruments and then identified in the ‘outcome’ GWAS. Effect estimates from individual genetic variants were combined with inverse-variance weighted regression and five sensitivity analyses were applied (weighted median, weighted mode, MR-Egger, generalized summary-data-based MR, and Steiger filtering).ResultsWe found strong evidence that liability to ADHD increases likelihood of smoking initiation and also cigarettes per day among smokers, decreases likelihood of smoking cessation, and increases likelihood of cannabis initiation and CUD. In the other direction, there was evidence that liability to smoking initiation and CUD increase ADHD risk. There was no clear evidence of causal effects between liability to ADHD and alcohol or caffeine consumption.ConclusionsWe find evidence for causal effects of liability to ADHD on smoking and cannabis use, and of liability to smoking and cannabis use on ADHD risk, indicating bidirectional pathways. Further work is needed to explore causal mechanisms.

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Association Between Mothers’ Alcohol Use Histories and Deficient Parenting in an Economically Disadvantaged Sample

Child Maltreatment ◽

10.1177/1077559520925550 ◽

2020 ◽

pp. 107755952092555

Author(s):

Sarah M. Taber-Thomas ◽

John F. Knutson

Keyword(s):

Substance Use ◽

Alcohol Use ◽

Child Maltreatment ◽

Low Socioeconomic Status ◽

Economically Disadvantaged ◽

Parenting Practices ◽

Structural Equation ◽

Equation Modeling ◽

Maternal Alcohol ◽

Inconsistent Discipline

Objective: Problematic maternal alcohol use confers risk for child maltreatment, though the effect on specific aspects of parenting is unclear. This study examined concurrent and prospective links among maternal alcohol use history, care neglect, supervisory neglect, and harsh or inconsistent discipline. Method: Multimethod multisource data were utilized to assess deficient parenting in 311 economically disadvantaged mothers at high risk of child maltreatment. Structural equation modeling was used to test hypothesized relations. Results: Maternal history of alcohol use was associated with more inconsistent discipline and higher levels of subsequent supervisory neglect. Secondary analyses among two-parent families found that paternal substance misuse was associated with maternal care neglect and poor supervision. Conclusions: Among low socioeconomic status families, maternal alcohol use increases the risk of inconsistent discipline and inadequate supervision. Inconsistent discipline may also lead to punitive parenting practices. Given the potential effect of paternal substance use on maternal parenting, findings highlight the importance of screening all caregivers for substance use in child welfare and research contexts to clarify when and how to intervene most effectively.

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