| Title: | Cannabis use, depression and self-harm: phenotypic and genetic relationships |
| Journal: | Addiction |
| Published: | 12 Dec 2019 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/31833150/ |
| DOI: | https://doi.org/10.1111/add.14845 |
| URL: | https://www.biorxiv.org/content/biorxiv/early/2019/02/14/549899.full.pdf |
Publication 2892
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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 is unclear. This study aimed to estimate the phenotypic and genetic associations between cannabis use and depression and self-harm.</p>
DESIGN: Cross-sectional data collected through UK Biobank were used to test the phenotypic association between cannabis use, depression and self-harm. UK Biobank genetic data were then combined with consortia genome-wide association study summary statistics to further test the genetic relationships between these traits using LD score regression, polygenic risk scoring and Mendelian randomization methods.</p>
SETTING: United Kingdom, with additional international consortia data.</p>
PARTICIPANTS: A total of 126 291 British adults aged between 40 and 70 years, recruited into UK Biobank.</p>
MEASUREMENTS: Phenotypic outcomes were life-time history of cannabis use (including initial and continued cannabis use), depression (including single-episode and recurrent depression) and self-harm. Genome-wide genetic data were used and assessment centre, batch and the first six principal components were included as key covariates when handling genetic data.</p>
FINDINGS: In UK Biobank, cannabis use is associated with an increased likelihood of depression [odds ratio (OR) = 1.64, 95% confidence interval (CI) = 1.59-1.70] and self-harm (OR = 2.85, 95% CI = 2.69-3.01). The strength of this phenotypic association is stronger when more severe trait definitions of cannabis use and depression are considered. Using consortia genome-wide summary statistics, significant genetic correlations are seen between cannabis use and depression [rg = 0.289, standard error (SE) = 0.036]. Polygenic risk scores for cannabis use and depression 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 randomization analyses were not significant.</p>
CONCLUSIONS: Cannabis use appeared to be both phenotypically and genetically associated with depression and self-harm. Limitations in statistical power mean that conclusions could not be made on the direction of causality between these traits.</p>
18 Keywords
- Adult
- Aged
- Biological Specimen Banks
- Cannabis
- Cross-Sectional Studies
- Depression
- Female
- Genome-Wide Association Study
- Humans
- Lod Score
- Male
- Marijuana Use
- Mendelian Randomization Analysis
- Middle Aged
- Multifactorial Inheritance
- Phenotype
- Self-Injurious Behavior
- United Kingdom
10 Authors
- Karen Hodgson
- Jonathan R. I. Coleman
- Saskia P. Hagenaars
- Kirstin L. Purves
- Kylie Glanville
- Shing Wan Choi
- Paul O'Reilly
- Gerome Breen
- Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium
- Cathryn M. Lewis
1 Application
| Application ID | Title |
|---|---|
| 18177 | Multi-trait GWAS analyses in the UK Biobank |
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