Abstract
Background and 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 between 40 and 70 years, recruited into UK Biobank
Measurements Genome-wide genetic data, phenotypic data on lifetime history of cannabis use, depression and self-harm.
Findings 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, 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 significant proportion of variance in cannabis use, depression and self harm within a UK Biobank target sample. However, two-sample Mendelian randomisation analyses were not significant.
Conclusions 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.
Footnotes
Declaration of competing interests: No competing interests to be declared.
