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Published January 1, 2022 | Version v1
Journal article Open

Clinical, environmental, and genetic risk factors for substance use disorders: characterizing combined effects across multiple cohorts

Creators

  • 1. Virginia Commonwealth Univ, Dept Human & Mol Genet, Richmond, VA USA
  • 2. Rutgers State Univ, Robert Wood Johnson Med Sch, Dept Psychiat, Piscataway, NJ USA
  • 3. Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Dept Psychiat, Richmond, VA USA
  • 4. Leiden Univ, Dept Econ, Leiden, Netherlands
  • 5. RTI Int, Biostat & Epidemiol Div, Durham, NC USA
  • 6. Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA
  • 7. SUNY Downstate Hlth Sci Univ, Dept Psychiat & Behav Sci, Brooklyn, NY 11203 USA
  • 8. Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland
  • 9. Univ Iowa, Dept Psychiat, Carver Coll Med, Iowa City, IA 52242 USA

Description

Substance use disorders (SUDs) incur serious social and personal costs. The risk for SUDs is complex, with risk factors ranging from social conditions to individual genetic variation. We examined whether models that include a clinical/environmental risk index (CERI) and polygenic scores (PGS) are able to identify individuals at increased risk of SUD in young adulthood across four longitudinal cohorts for a combined sample of N = 15,134. Our analyses included participants of European (N-EUR = 12,659) and African (N-AFR = 2475) ancestries. SUD outcomes included: (1) alcohol dependence, (2) nicotine dependence; (3) drug dependence, and (4) any substance dependence. In the models containing the PGS and CERI, the CERI was associated with all three outcomes (ORs = 01.37-1.67). PGS for problematic alcohol use, externalizing, and smoking quantity were associated with alcohol dependence, drug dependence, and nicotine dependence, respectively (OR = 1.11-1.33). PGS for problematic alcohol use and externalizing were also associated with any substance dependence (ORs = 1.09-1.18). The full model explained 6-13% of the variance in SUDs. Those in the top 10% of CERI and PGS had relative risk ratios of 3.86-8.04 for each SUD relative to the bottom 90%. Overall, the combined measures of clinical, environmental, and genetic risk demonstrated modest ability to distinguish between affected and unaffected individuals in young adulthood. PGS were significant but added little in addition to the clinical/environmental risk index. Results from our analysis demonstrate there is still considerable work to be done before tools such as these are ready for clinical applications.

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