Genetic Risk Scores for Cannabis Disorder Did Not Predict When African American Youth Started Using

Cannabis use disorder and nicotine dependence polygenic risk scores were not associated with initiation of these substances. Unexpectedly, higher alcohol use disorder PRS predicted later alcohol initiation (HR 0.78). For cannabis, high parental monitoring was associated with earlier initiation among those with high genetic risk, while low monitoring predicted earlier initiation among those with low genetic risk.

Longitudinal study of 1,017 African American participants (56% female) from an elementary school prevention trial. At age 20, substance initiation ages were reported and genetic samples collected. At age 12, parental monitoring and census-tract disadvantage were measured. Cox Proportional Hazard Models tested PRS and environment interactions.

Most genetic risk studies are conducted in European-ancestry populations. This study provides critical data on whether polygenic risk scores derived from current research predict substance use in African American youth, where they largely did not.

The null findings for CUD and nicotine PRS suggest current genetic risk scores may not transfer well across ancestry groups, highlighting the need for more diverse GWAS studies. The unexpected monitoring interaction challenges simple models of genetic and environmental risk.

PRS derived largely from European-ancestry GWAS may perform poorly in African American populations. Self-reported initiation ages subject to recall bias. Parental monitoring measured at age 12 may not capture later changes. Single geographic region.