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Addiction. 2019 Dec 12. doi: 10.1111/add.14845. [Epub ahead of print]

Cannabis use, depression and self-harm: phenotypic and genetic relationships.

Author information

1
Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
2
NIHR Maudsley Biomedical Research Centre, South London and Maudsley NHS Trust, London, UK.
3
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

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.

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.

SETTING:

United Kingdom, with additional international consortia data.

PARTICIPANTS:

A total of 126 291 British adults aged between 40 and 70 years, recruited into UK Biobank.

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.

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.

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.

KEYWORDS:

Cannabis use; Mendelian randomization; UK biobank; depression; genetic correlation; genetics; heritability; polygenic risk; self-harm

PMID:
31833150
DOI:
10.1111/add.14845

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