Background: Cannabis use (CU) is an etiologically complex behavior with several social, temperamental, neurocognitive, and behavioral precursors. Biometrical and molecular studies suggest an interplay of environmental and pleiotropic genetic influences. However, it remains unclear whether identified genetic effects related to behavioral and temperamental characteristics have developmentally direct or indirect mechanisms on CU behavior. The Transmissible Liability Index (TLI) is a measure of continuous liability based on developmental precursors of substance use disorders (e.g., antisocial behavior, disruptive disorders, disinhibited personality traits, internalizing/externalizing characteristics) and may play a role in understanding genetic risk for CU.Methods: We interrogated the polygenic effects of several internalizing/externalizing behaviors on the TLI (derived from adolescent traits and behaviors) and CU (initiation and repeated use) in emerging adulthood using a homogeneous sample of 4077 individuals of European Ancestry. Summary statistics from discovery genome-wide association studies of cannabis use, risk tolerance, neuroticism, anxiety, and depression were used to construct polygenic scores (PGSs) that were used to predict CU. Mediation analyses assessed whether behavioral and temperamental traits exhibited during adolescence, as captured via the TLI, accounted for the association between PGSs and CU.Results: The marker-based heritability of TLI, CU initiation, and repeated CU were modest (14%, p=0.033; 15%, p=0.025; and 17%, p=0.008, respectively). TLI and repeated CU were genetically correlated (0.76, p=0.033). Among the PGSs, risk tolerance, neuroticism, and depression were associated with higher TLI. Mediation analyses indicated significant, but very modest, indirect effects of risk tolerance and depression on repeated CU. Conclusions: Adolescent behavioral and temperamental characteristics are early indicators of repeated cannabis use in adulthood. Polygenic risk for cannabis use does not appear to increase risk for later cannabis use. Polygenic risk for internalizing/externalizing traits may act through behaviors and traits exhibited during adolescence (i.e., the transmissible liability index) to increase risk for cannabis use.