Age at first use and later substance use disorder: Shared genetic and environmental pathways for nicotine, alcohol, and cannabis.
- Authors
- Richmond-Rakerd, Leah S; Slutske, Wendy S; Lynskey, Michael T; Agrawal, Arpana; Madden, Pamela A F; Bucholz, Kathleen K; Heath, Andrew C; Statham, Dixie J; Martin, Nicholas G
- Year
- 2016
- Journal
- Journal of abnormal psychology
- PMID
- 27537477
- DOI
- 10.1037/abn0000191
- PMCID
- PMC5061603
Behavioral genetic studies have provided insights into why early substance use initiation is associated with increased risk for disorder. Few genetically informative studies, however, have operationalized initiation as the timing of first use and simultaneously modeled the timing of initiation and problematic use of multiple substances. Such research can help capture the risk associated with early initiation and determine the extent to which genetic and environmental risk generalizes across substances. This study utilized a behavior genetic approach to examine the relation between the age of substance use initiation and symptoms of substance use disorder. Participants were 7,285 monozygotic and dizygotic twins (40% male, mean age at interview = 30.6 years) from the Australian Twin Registry who reported on their ages of tobacco, alcohol, and cannabis initiation and symptoms of Diagnostic and Statistical Manual of Mental Disorders (4th ed., DSM-IV) nicotine dependence, alcohol use disorder, and cannabis use disorder. Biometric modeling was conducted to (a) determine the structure of genetic and environmental influences on initiation and disorder and (b) examine their genetic and environmental overlap. The latent structure of initiation differed across men and women. The familial covariance between initiation and disorder was genetic among men and genetic and environmental among women, suggesting that the relation between first substance use and disorder is partly explained by a shared liability. After accounting for familial overlap, significant unique environmental correlations were observed, indicating that the age of initiation of multiple drugs may directly increase risk for substance-related problems. Results support the utility of conceptualizing initiation in terms of age and of adopting a multivariate approach. (PsycINFO Database Record
Independent pathway model for the ages of tobacco, alcohol, and cannabis initiation. For ease of presentation, this path diagram represents only one twin in a pair. Unprimed factors are common to all three substances and primed factors are specific to each substance. A=additive genetic, C=shared environment, E=unique environment.
Common pathway model for the ages of tobacco, alcohol, and cannabis initiation. For ease of presentation, this path diagram represents only one twin in a pair. Unprimed factors are common to all three substances and primed factors are specific to each substance. A=additive genetic, C=shared environment, E=unique environment.
Bivariate factor model for the ages of tobacco, alcohol, and cannabis initiation and nicotine dependence, alcohol use disorder, and cannabis use disorder. For ease of presentation, this path diagram represents only one twin in a pair. Unprimed factors are common to all three substances and primed factors are specific to each substance. A=additive genetic, C=shared environment, E=unique environment. rG=genetic correlation, rC=shared environmental correlation, rE=unique environmental correlation.
Standardized parameter estimates for the bivariate factor model for men. The positive correlations between the factors are due to reverse scoring the age of initiation variables. Note that although the shared environmental correlation looks high, it is not statistically significant. 95% confidence limits presented in brackets. A=additive genetic, C=shared environment, E=unique environment. rG=genetic correlation, rC=shared environmental correlation, rE=unique environmental correlation.
Standardized parameter estimates for the bivariate factor model for women. The positive correlations between the factors are due to reverse scoring the age of initiation variables. 95% confidence limits presented in brackets. A=additive genetic, C=shared environment, E=unique environment. rG=genetic correlation, rC=shared environmental correlation, rE=unique environmental correlation.
| Name | Type |
|---|---|
| abstainers | phenotype |
| addiction | phenotype |
| adolescent substance use | phenotype |
| age | phenotype |
| AgeAtFirstSubstanceUse local | phenotype |
| age at initiation | phenotype |
| Age of cigarette initiation local | phenotype |
| Age of first substance use local | phenotype |
| alcohol | phenotype |
| Alcohol abstinence | phenotype |
| alcohol abuse | phenotype |
| alcohol dependence | phenotype |
| Alcohol Initiation | phenotype |
| Alcohol Use | phenotype |
| Alcohol Use Disorder | phenotype |
| assessment year | phenotype |
| AUD | phenotype |
| Australian Twin Registry Cohort II local | cohort |
| Australian Twin Registry Cohort III local | cohort |
| beer | drug |
| behavioral disinhibition | phenotype |
| birth year | phenotype |
| cannabis abstainer local | phenotype |
| cannabis abstention local | phenotype |
| cannabis dependence | phenotype |
| cannabis initiation | phenotype |
| Cannabis initiation age local | phenotype |
| cannabis use | phenotype |
| cannabis use disorder | phenotype |
| childhood conduct disorder | phenotype |
| cigarettes | phenotype |
| Cohort III local | cohort |
| combined sample | cohort |
| Common pathway model local | phenotype |
| Common shared environmental factor local | phenotype |
| Common unique environmental factor local | phenotype |
| common variants | cohort |
| Comorbid disorders local | phenotype |
| comorbid substance use problems local | phenotype |
| conduct disorder | phenotype |
| CPM local | cohort |
| CUD | phenotype |
| current study | cohort |
| disorder | phenotype |
| DSM-IV cannabis abuse | phenotype |
| DSM-IV cannabis dependence | phenotype |
| DSM-IV CUD symptom count local | phenotype |
| DSM-IV nicotine dependence | phenotype |
| early first substance use local | phenotype |
| early initiation | phenotype |
| Early-Initiation Phenotypes local | phenotype |
| early polysubstance initiation local | phenotype |
| early substance use | phenotype |
| Early substance use uptake local | phenotype |
| Familial liability to early substance involvement local | phenotype |
| Family Environmental Factors local | phenotype |
| first substance use local | phenotype |
| First use of multiple substances local | phenotype |
| full sample | cohort |
| Heavy and Problematic Use local | phenotype |
| independent pathway model | phenotype |
| initiation | phenotype |
| IPM local | cohort |
| Latent factor local | drug |
| Latent phenotype initiation local | phenotype |
| later abuse/dependence local | phenotype |
| later comorbid substance use problems local | phenotype |
| lifetime alcohol use | phenotype |
| Lifetime cannabis users local | phenotype |
| LifetimeSubstanceUse local | phenotype |
| Lifetime tobacco users local | phenotype |
| men | cohort |
| multiple drugs | drug |
| nicotine | drug |
| nicotine dependence | phenotype |
| Parental attitudes toward substance use local | phenotype |
| parental divorce/separation | phenotype |
| participants | cohort |
| peer deviance | phenotype |
| Perceived Availability of Cannabis local | phenotype |
| physical abuse | phenotype |
| polysubstance abuse | phenotype |
| Polysubstance involvement local | phenotype |
| problematic use | phenotype |
| problem cannabis use | phenotype |
| Regular drinkers local | phenotype |
| sex | phenotype |
| shared environmental influence | phenotype |
| singletons | cohort |
| smoking | phenotype |
| spirits | drug |
| study cohort | cohort |
| substance | phenotype |
| substance abuse | phenotype |
| substance use | phenotype |
| symptom count | phenotype |
| Symptoms of later substance use disorder local | phenotype |
| symptoms of substance use disorder local | phenotype |
| Timing of initiation of multiple drugs local | phenotype |
| tobacco abstainer local | phenotype |
| tobacco abstention local | phenotype |
| tobacco initiation | phenotype |
| tobacco use | phenotype |
| Tolerance to nicotine local | phenotype |
| Twin cohort | cohort |
| twin pair cohort local | cohort |
| Unique environmental liability to early substance involvement local | phenotype |
| wine | drug |
| women | cohort |
| Year of assessment local | phenotype |
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