The interplay between externalizing disorders polygenic risk scores and contextual factors on the development of marijuana use disorders.

Externalizing disorders have been extensively linked to substance use problems. However, less is known about whether genetic factors underpinning externalizing disorders and environmental features interact to predict substance use disorders (i.e., marijuana abuse and dependence) among urban African Americans. We examined whether polygenic risk scores (PRS) for conduct disorder (CD) and attention-deficit hyperactivity disorder (ADHD) interacted with contextual factors (i.e., parental monitoring, community disadvantage) to influence risk for marijuana use disorders in a sample of African American youth. Participants (N=1,050; 44.2% male) were initially recruited for an elementary school-based universal prevention trial in a Mid-Atlantic city and followed through age 20. Participants reported on their parental monitoring in sixth grade and whether they were diagnosed with marijuana abuse or dependence at age 20. Blood or saliva samples were genotyped using the Affymetrix 6.0 microarrays. The CD and ADHD PRS were created based on genome-wide association studies conducted by Dick et al. (2010) and Demontis et al. (2017), respectively. Community disadvantage was calculated based on census data when participants were in sixth grade. There was an interaction between the CD PRS and community disadvantage such that a higher CD PRS was associated with greater risk for a marijuana use disorder at higher levels of neighborhood disadvantage. This finding should be interpreted with caution owing to the number of significance tests performed. Implications for etiological models and future research directions are presented.