Polygenic risk scores represent aggregated effects across the many loci associated with a disorder at p-value thresholds that accommodate tens of thousands of SNPs, thus approximating additive genetic variance (12). Polygenic risk scores are generated using a discovery genetic association study of one disorder (e.g. schizophrenia meta-analysis) and can be applied to compute the phenotypic variance explained by the score in a new independent sample. For example, polygenic risk scores were used to show that schizophrenia has underlying shared genetic liability with bipolar disorder (12–17) and major depressive disorder (18). Importantly, a growing number of studies have begun to investigate shared genetic liability between schizophrenia and patterns of substance use. We recently found a statistically significant association between general liability for substance use disorder and polygenic risk for cross-disorder psychopathology (19). In addition, recent studies have described common genetic risk factors between schizophrenia and cannabis use (20, 21), and evidence for shared genetic factors between schizophrenia and smoking-related phenotypes (22, 23).
