Dataset Information

Associations between polygenic risk of substance use and use disorder and alcohol, cannabis, and nicotine use in adolescence and young adulthood in a longitudinal twin study.

ABSTRACT:

Background

Recent well-powered genome-wide association studies have enhanced prediction of substance use outcomes via polygenic scores (PGSs). Here, we test (1) whether these scores contribute to prediction over-and-above family history, (2) the extent to which PGS prediction reflects inherited genetic variation v. demography (population stratification and assortative mating) and indirect genetic effects of parents (genetic nurture), and (3) whether PGS prediction is mediated by behavioral disinhibition prior to substance use onset.

Methods

PGSs for alcohol, cannabis, and nicotine use/use disorder were calculated for Minnesota Twin Family Study participants (N = 2483, 1565 monozygotic/918 dizygotic). Twins' parents were assessed for histories of substance use disorder. Twins were assessed for behavioral disinhibition at age 11 and substance use from ages 14 to 24. PGS prediction of substance use was examined using linear mixed-effects, within-twin pair, and structural equation models.

Results

Nearly all PGS measures were associated with multiple types of substance use independently of family history. However, most within-pair PGS prediction estimates were substantially smaller than the corresponding between-pair estimates, suggesting that prediction is driven in part by demography and indirect genetic effects of parents. Path analyses indicated the effects of both PGSs and family history on substance use were mediated via disinhibition in preadolescence.

Conclusions

PGSs capturing risk of substance use and use disorder can be combined with family history measures to augment prediction of substance use outcomes. Results highlight indirect sources of genetic associations and preadolescent elevations in behavioral disinhibition as two routes through which these scores may relate to substance use.

SUBMITTER: Schaefer JD

PROVIDER: S-EPMC10123833 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Publications

Associations between polygenic risk of substance use and use disorder and alcohol, cannabis, and nicotine use in adolescence and young adulthood in a longitudinal twin study.

Schaefer Jonathan D JD Jang Seon-Kyeong SK Clark D Angus DA Deak Joseph D JD Hicks Brian M BM Iacono William G WG Liu Mengzhen M McGue Matt M Vrieze Scott I SI Wilson Sylia S

Psychological medicine 20211012 6

<h4>Background</h4>Recent well-powered genome-wide association studies have enhanced prediction of substance use outcomes via polygenic scores (PGSs). Here, we test (1) whether these scores contribute to prediction over-and-above family history, (2) the extent to which PGS prediction reflects inherited genetic variation <i>v.</i> demography (population stratification and assortative mating) and indirect genetic effects of parents (genetic nurture), and (3) whether PGS prediction is mediated by b ...[more]

PMID: 37310313

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Project description:Background and aimsMolecular genetic studies of alcohol and nicotine use have identified many genome-wide association study (GWAS) loci. We measured associations between drinking and smoking polygenic scores (PGS) and trajectories of alcohol and nicotine use outcomes from late childhood to early adulthood, substance-specific versus broader-liability PGS effects, and if PGS performance varied for consumption versus problematic substance use.Design, setting, participants and measurementsWe fitted latent growth curve models with structured residuals to scores on measures of alcohol and nicotine use and problems from ages 14 to 34 years. We then estimated associations between the intercept (initial status) and slope (rate of change) parameters and PGSs for drinks per week (DPW), problematic alcohol use (PAU), cigarettes per day (CPD) and ever being a regular smoker (SMK), controlling for sex and genetic principal components. All data were analyzed in the United States. PGSs were calculated for participants of the Minnesota Twin Family Study (n = 3225) using results from the largest GWAS of alcohol and nicotine consumption and problematic use to date.FindingsEach PGS was associated with trajectories of use for their respective substances [i.e. DPW (βmean = 0.08; βrange = 0.02-0.12) and PAU (βmean = 0.12; βrange = -0.02 to 0.31) for alcohol; CPD (βmean = 0.08; βrange = 0.04-0.14) and SMK (βmean = 0.18; βrange = 0.05-0.36) for nicotine]. The PAU and SMK PGSs also exhibited cross-substance associations (i.e. PAU for nicotine-specific intercepts and SMK for alcohol intercepts and slope). All identified SMK PGS effects remained as significant predictors of nicotine and alcohol trajectories (βmean = 0.15; βrange = 0.02-0.33), even after adjusting for the respective effects of all other PGSs.ConclusionsSubstance use-related polygenic scores (PGSs) vary in the strength and generality versus specificity of their associations with substance use and problems over time. The regular smoking PGS appears to be a robust predictor of substance use trajectories and seems to measure both nicotine-specific and non-specific genetic liability for substance use, and potentially externalizing problems in general.

Project description:ImportanceLittle is known about cannabis vaping trajectories across adolescence and young adulthood or the co-occurrence with nicotine vaping.ObjectiveTo evaluate nicotine vaping and cannabis vaping trajectories from late adolescence to young adulthood (≥18 years of age) and the extent of polysubstance vaping.Design, setting, and participantsIn this prospective cohort study, 5 surveys (including information on substance vaped) were completed at 10 high schools in the Los Angeles, California, metro area. Students were surveyed at 6-month intervals from fall of 11th grade (October to December 2015; wave 5) through spring of 12th grade (March to June 2017; wave 8) and again approximately 1 to 2 years after high school (October 2018 to October 2019; wave 9).ExposuresPast 30-day nicotine and cannabis vaping frequency across 5 waves.Main outcomes and measuresSelf-reported frequency of nicotine vaping and cannabis vaping within the past 30 days across 5 time points from late adolescence to young adulthood. Trajectories were measured with these past 30-day use frequencies at each wave. Parallel growth mixture modeling estimated conditional probabilities of polysubstance vaping.ResultsThe analytic sample included 3322 participants with at least 1 time point of data (mean [SD] age, 16.50 [0.42] years at baseline; 1777 [53.5%] female; 1573 [47.4%] Hispanic or Latino). Growth mixture modeling identified the 5-trajectory model as optimal for both nicotine vaping and cannabis vaping. Trajectories for nicotine and cannabis vaping were similar (nonusers: 2246 [67.6%] nicotine, 2157 [64.9%] cannabis; infrequent users: 566 [17.0%] nicotine, 608 [18.3%] cannabis; moderate users: 167 [5.0%] nicotine, 233 [7.0%] cannabis; young adult-onset frequent users: 213 [6.4%] nicotine, 190 [5.7%] cannabis; adolescent-onset escalating frequent users: 131 [3.9%] nicotine, 134 [4.0%] cannabis). Males had greater odds of belonging to the adolescent-onset escalating frequent users nicotine (adjusted odds ratio, 2.88; 95% CI, 1.58-5.23; P < .01) and cannabis (adjusted odds ratio, 1.95; 95% CI,1.03-3.66; P < .05) vaping trajectories compared with nonusers. Polysubstance vaping was common, with those in trajectories reflecting more frequent nicotine vaping (adolescent-onset escalating frequent users and young adult-onset frequent users) having a high probability of membership (85% and 93%, respectively) in a cannabis-use trajectory.Conclusions and relevanceIn this cohort study, the prevalence and type of nicotine vaping and cannabis vaping developmental trajectories from late adolescence to young adulthood were similar. Polysubstance vaping was common from late adolescence to young adulthood, particularly among those reporting more frequent vaping use. The findings suggest that public health policy and clinical interventions should address polysubstance vaping in both adolescence and young adulthood.

Dataset Information

Associations between polygenic risk of substance use and use disorder and alcohol, cannabis, and nicotine use in adolescence and young adulthood in a longitudinal twin study.

Background

Methods

Results

Conclusions

Publications

Associations between polygenic risk of substance use and use disorder and alcohol, cannabis, and nicotine use in adolescence and young adulthood in a longitudinal twin study.

Similar Datasets

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