Polygenic risk scores (PRS) did not predict the development of cannabis use disorder (CUD) in patients with schizophrenia and other psychiatric disorders, according to results from a study published in Psychological Medicine.

Researchers conducted a case-control study to examine the associations between PRS for schizophrenia and other mental disorders with the development of CUD. The retrospective analysis included 3 groups (N=88,637): patients with schizophrenia (n=3533; 55.9% men; mean age of onset, 21.5 years), patients with other mental disorders (n=56,393; 53.9% men; mean age of onset, 15.6 years), and nonpsychiatric control patients (n=28,711; 50.9% men). Data were obtained from iPSYCH data set, which combines Danish registry information with genetic data collected from dried neonatal bloodspots. PRS exposures of interest were autism spectrum disorder, anorexia nervosa, attention-deficit/hyperactivity disorder (ADHD), and schizophrenia; the key outcome of interest was diagnosis of CUD.

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The researchers found that PRS for schizophrenia were not associated with the development of CUD in control subjects (hazard ratio [HR], 1.16; 95% CI, 0.95-1.43). In contrast, the PRS for ADHD did predict CUD in controls (HR, 1.27; 95% CI, 1.08-1.50).

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With regard to anorexia nervosa and autism spectrum disorder, the PRS did not predict CUD in any of the groups, with the exception of an inverse association between CUD and PRS for autism spectrum disorder and anorexia nervosa in patients with other mental disorders (HR, 0.95 [95% CI, 0.92-0.99] and HR, 1.13 [95% CI, 1.00-1.27], respectively). In the group with schizophrenia, there was an association between PRS and CUD, and prior diagnosis of CUD was a strong predictor of developing schizophrenia (HR, 4.91; 95% CI, 4.36-5.53).

“If the findings of our study are correct, this would then counter one of the most often used arguments against the theory of cannabis being a component cause of schizophrenia,” the researchers wrote. They noted, however, that the study was limited by its observational design and difficulty capturing cannabis use in registry data.

The investigators concluded that “results in the present study speak against the hypothesis that the association between cannabis use and later development of schizophrenia is caused by a common genetic vulnerability.”


Hjorthøj C, Uddin MJ, Wimberley T, et al. No evidence of associations between genetic liability for schizophrenia and development of cannabis use disorder [published online December 9, 2019]. Psychol Med. doi:10.1017/S0033291719003362