Evidence of strong genetic correlations among SUDs and externalizing phenotypes suggests that further investigation into their shared genetic architecture is warranted. Recent advances in statistical genetics methods allow us to leverage summary statistics from well-powered genome-wide association studies (GWAS) to model the degree to which genetic influences on individual, related phenotypes operate through broad latent factors that represent the variance shared among these phenotypes. Specifically, genomic structural equation modelling (genomic SEM)18 provides a flexible framework to apply SEM techniques to genetic covariance matrices derived from linkage disequilibrium score regression.19 This allows researchers to formally test theoretical models of the shared genetic architecture of genetically correlated traits.
