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Published on: August 18, 2020
Genetics of cannabis use in opioid use disorder: A genome-wide association and polygenic risk score study
Alannah Hillmer1, Caroul Chawar1, Amel Lamri2
1Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada.
Background:
Individuals with an Opioid Use Disorder (OUD) have increased rates of cannabis use in comparison to the general population. Research on the short- and long-term impacts of cannabis use in OUD patients has been inconclusive. A genetic component may contribute to cannabis cravings.
Aims:
Identify genetic variants associated with cannabis use through Genome-wide Association Study (GWAS) methods and investigate a Polygenic Risk Score (PRS). In addition, we aim to identify any sex differences in effect size for genetic variants reaching or nearing genome-wide significance in the GWAS.
Methods:
The study outcomes of interest were: regular cannabis use (yes/no) (n = 2616), heaviness of cannabis use (n = 1293) and cannabis cravings (n = 836). Logistic and linear regressions were preformed, respectively, to test the association between genetic variants and each outcome, regular cannabis use and heaviness of cannabis use. GWAS summary statistics from a recent large meta-GWAS investigating cannabis use disorder were used to conduct PRS's. Findings are limited to a European ancestry sample.
Results:
No genome-wide significant associations were found. Rs1813412 (chromosome 17) for regular cannabis use and rs62378502 (chromosome 5) for heaviness of cannabis use were approaching genome-wide significance. Both these SNPs were nominally significant (p<0.05) within males and females, however sex did not modify the association. The PRS identified statistically significant association with cannabis cravings. The variance explained by all PRSs were less than 1.02x10-2.
Conclusion:
This study provides promising results in understanding the genetic contribution to cannabis use in individuals living with OUD.
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