The Interplay between a Conduct Disorder Polygenic Risk Score and Community Disadvantage in Predicting Marijuana Use Disorders

• In Event: 1-125 - Genetically-Informed Studies of Adolescent Substance Use and Psychopathology

Integrative Statement

Aim: Marijuana use and disorders are major public health problems that have been widely studied. Conduct disorder (CD) and community disadvantage have been independently predictive of marijuana use, abuse, and dependence. However, less is known about whether genetic factors associated with CD and community disadvantage jointly influence risk for marijuana use problems. We examined whether a conduct disorder polygenic risk score (CD PRS) interacted with community disadvantage to predict lifetime marijuana use and marijuana use disorders.

Method: Participants (N=1,050, 43.9% male) were initially recruited for an elementary school-based universal prevention trial in a Mid-Atlantic city and followed through age 20. Youth reported on their substance use in adulthood. Blood or saliva samples were genotyped using the Affymetrix 6.0 microarrays. A CD PRS was created based on a genome-wide association study conducted by Dick et al., 2010. Community disadvantage was calculated based on census data when youth were in sixth grade. Logistic regressions were conducted to investigate the main effects of the predictor variables on lifetime marijuana use and marijuana abuse or dependence. The sample was restricted to African Americans given the possibility of population stratification.

Results: There was an interaction between youth’s CD PRS and community disadvantage in predicting marijuana use disorders. In particular, youth with a higher CD PRS exhibited greater risk for a marijuana use disorder when exposed to higher neighborhood disadvantage. The interaction between youth’s CD PRS and neighborhood disadvantage in predicting lifetime marijuana use was not significant.

Conclusion: Among youth with a higher CD PRS, neighborhoods higher in disadvantage may facilitate marijuana use disorders, possibly because of greater availability of drugs and reduced access to services aimed at attenuating substance use disorders in these communities (Shanahan & Hofer, 2005). Intervention efforts aimed at attenuating marijuana use problems should consider targeting areas higher in disadvantage, as these areas may facilitate drug use among African-American youth with higher genetic loading for CD.

Authors

• Jill A. Rabinowitz, Johns Hopkins University
  Presenting Author

• Rashelle Jean Musci, Johns Hopkins Bloomberg School of Public Health
  Non-Presenting Author

• Adam Milam, Johns Hopkins University
  Non-Presenting Author

• Kelly Benke, Johns Hopkins University
  Non-Presenting Author

• Danielle Y. Sisto, Johns Hopkins University
  Non-Presenting Author

• Nicholas S. Lalongo, Johns Hopkins University
  Non-Presenting Author

• Brion S. Maher, Johns Hopkins University
  Non-Presenting Author

• George Uhl, New Mexico VA HealthCare System
  Non-Presenting Author