“Cannabis Use, Depression and Self-Harm: Phenotypic and Genetic Relationships”, 2019-02-14 (; similar):
Background & Aims
The use of cannabis has previously been linked to both depression and self-harm, however the role of genetics in this relationship are unclear. We aimed to examine the phenotypic and genetic relationships between these traits.
Design: Genetic and cross-sectional phenotypic data collected through UK Biobank, together with consortia genome-wide association study summary statistics. These data were used to assess the phenotypic and genetic relationship between cannabis use, depression and self harm.
Setting: UK, with additional international consortia data
Participants: N=126,291 British adults aged 40–70 years, recruited into UK Biobank
Measurements: Genome-wide genetic data, phenotypic data on lifetime history of cannabis use, depression and self-harm.
Results
In UK Biobank, cannabis use is associated with increased likelihood of depression (OR=1.64, 95% CI = 1.59–1.70, p = 1.19×10−213) and self-harm (OR=2.85, 95% CI = 2.69–3.01, p = 3.46×10−304). The strength of this phenotypic association is stronger when more severe trait definitions of cannabis use and depression are considered. Additionally, statistically-significant genetic correlations are seen between cannabis use and depression using consortia summary statistics (rg=0.289, SE=0.036, p = 1.45×10−15). Polygenic risk scores for cannabis use and depression both explain a small but proportion of variance in cannabis use, depression and self harm within a UK Biobank target sample. However, two-sample Mendelian Randomization analyses were not.
Conclusion: Cannabis use is both phenotypically and genetically associated with depression and self harm. Future work dissecting the causal mechanism linking these traits may have implications for cannabis users.