Our analysis has several important limitations. First, although we included individuals of diverse ancestries, the PGS for our samples of African ancestries were severely underpowered due to the small size of the discovery sample. Large-scale GWAS in diverse cohorts are vital to ensuring that any benefit of precision medicine is shared equitably across the population [63]. Second, while distinct, ancestry is related to race-ethnicity, and with it, racism and racial discrimination, some of the most profound social determinants of health [64]. Our measure of environmental risk was crude and may not fully capture risk factors that contribute to SUDs in populations beyond non-Hispanic Whites. Future studies should include racially relevant measures of risk (e.g., experiences of interpersonal racism/discrimination, racial residential segregation) as well as other social and environmental measures that are known risk factors for SUDs (e.g., neighborhood social conditions, alcohol outlet density). Further refinement of known risk factors may allow for better prediction of those at risk of developing an SUD. We did observe variation in the predictive ability of the CERI across cohorts, suggesting the observed effect may
