Building a Prediction Model to Detect Elevated Risk for Developing a Substance Use Disorder
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Importance
Preventing substance use disorder (SUD) is a top public health priority, but clinical practice currently lacks validated prognostic tools to identify risk before the onset of heavy use/problems.
Objective
To determine whether models can predict SUD using genetic, behavioral, and environmental factors and to evaluate performance across substance types (alcohol, cannabis, tobacco), sex, and genetic similarity groups.
Design
This prognostic study developed and validated a multi-domain risk model using data from four longitudinal cohorts (The National Longitudinal Study of Adolescent to Adult Health, Avon Longitudinal Study of Parents and Children, The Collaborative Study on the Genetics of Alcoholism, and FinnTwin12) with follow-up from early adolescence into young adulthood.
Setting
Population-based and family-based samples from the United States, United Kingdom, and Finland.
Participants
The analysis included participants with available genomic and behavioral data. The cohorts represented a spectrum of risk, ranging from nationally representative community samples to high-risk populations.
Exposure(s) (for observational studies)
Predictors included polygenic scores for substance use-related phenotypes and 10 established early-life behavioral and environmental risk factors.
Main Outcome(s) and Measure(s)
The outcomes were a diagnosis of moderate-to- severe SUD based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and positive and negative predictive value.
Results
A total of 16,362 participants were included in the study (54.7% female; mean [SD] age 26.73 [3.36]). Genetic similarity group composition was 70.4% European, 16.8% African, 9.8% admixed American, 2.2% East Asian, and 0.7% South Asian. SUD prevalence was 22.0%. The integrated model achieved an AUC of 0.78 for predicting any SUD, with a sensitivity of 69% and a positive predictive value of 45%. Performance was comparable for specific substances (AUC range 0.74–0.82) and across genetic similarity groups (AUC range 0.61-0.82). The model demonstrated higher AUC in females compared with males.
Conclusions and Relevance
Findings highlight the potential utility of an SUD prediction model to inform clinicians and patients about risk for developing a SUD.
Key points
Question
Can we develop prediction models to detect elevated risk for developing a substance use disorder (SUD) prior to onset.?
Findings
Using a harmonized dataset of four diverse longitudinal cohorts, we developed and evaluated a prediction model that integrates genetic, behavioral, and environmental predictors. The model demonstrated good discriminatory power to identify individuals at risk for future SUD.
Meaning
These findings establish a framework for integrating multi-domain, multiinformant data into clinical workflows, offering a basis for personalized risk stratification and prevention of SUDs.
