Psychotic patients who used cannabis frequently before illness onset have higher genetic predisposition to schizophrenia than those who did not

Background. Schizophrenia (SZ) and bipolar disorder (BD) are heritable, polygenic disorders with shared clinical and genetic components, suggesting a psychosis continuum. Cannabis use is a well-documented environmental risk factor in psychotic disorders. In the current study, we investigated the relationship between SZ genetic load and cannabis use before illness onset in SZ and BD spectrums. Since frequent early cannabis use (age < 18 years) is believed to increase the risk of developing psychosis more than later use, follow-up analyses were conducted comparing early use to later use and no use. Methods. We assigned a SZ-polygenic risk score (PGRS) to each individual in our independent sample (N = 381 SZ spectrum cases, 220 BD spectrum cases and 415 healthy controls), calculated from the results of the Psychiatric Genomics Consortium (PGC) SZ case-control study (N = 81 535). SZ-PGRS in patients who used cannabis weekly to daily in the period before first illness episode was compared with that of those who never or infrequently used cannabis. Results. Patients with weekly to daily cannabis use before illness onset had the highest SZ-PGRS (p = 0.02, Cohen's d = 0.33). The largest difference was found between patients with daily or weekly cannabis use before illness onset < 18 years of age and patients with no or infrequent use of cannabis (p = 0.003, Cohen's d = 0.42). Conclusions. Our study supports an association between high SZ-PGRS and frequent cannabis use before illness onset in psychosis continuum disorders.