Abstract

Background Cannabis is the most widely used illicit drug in the world. It is well established that substance abuse comorbidity i.a. cannabis use is much higher among patients with Schizophrenia (SCZ) and Bipolar Disorders (BD) than in the general population. However, the relationship between risk of SCZ, BD and cannabis use has not been completely understood so far. Previous studies have revealed that a genetic predisposition to SCZ might be associated with increased use of cannabis in healthy individuals. Given this relationship, we intended to study whether polygenic risk scores (PRS) for SCZ predict cannabis use in patients with SCZ and BD. In addition, we want to test whether BD PRS or Cannabis (CAN) PRS have an impact on cannabis use in these two subgroups. Methods The present study included the USA GAIN/TGEN sample (1.150 BD patients) and the German KFO/PsyCourse cohort (433 SCZ and 327 BD patients) (www.kfo241.de; www.PsyCourse.de). Information on ever/never use of cannabis was available in these samples. PRS were calculated as follows: For each SNP contributing to the PRS, the number of risk variants carried by an individual was multiplied by the logarithm of the odds ratio for that particular variant. The resulting values were summed up in an additive fashion obtaining a weighted individual estimate of the SCZ genetic burden in each individual at different p-value thresholds. The most recent summary statistics on SCZ GWAS (Ripke et al., 2014), BD GWAS (Hou et al., 2016) and Cannabis use (Sherva et al., 2016) were used to ascertain risk variants, their P-values, and associated odds ratios for the respective disorders. Results SCZ PRS were associated (P Discussion First results suggest that individuals with BD and an increased polygenic risk for SCZ are more likely to use cannabis. The association between BD and cannabis use might be not simply one of an environmental risk factor, but rather involves gene–environment interaction, as individuals choose and shape their own environment according on their own innate preferences.

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