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.

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大麻使用、抑郁和自残：表型和遗传关系

背景和目的 以前大麻的使用与抑郁和自残有关；然而，遗传在这种关系中的作用尚不清楚。本研究旨在估计大麻使用与抑郁和自残之间的表型和遗传关联。设计 通过英国生物银行收集的横断面数据用于测试大麻使用、抑郁和自残之间的表型关联。然后将 UK Biobank 遗传数据与联盟全基因组关联研究汇总统计数据相结合，以使用 LD 评分回归、多基因风险评分和孟德尔随机化方法进一步测试这些性状之间的遗传关系。设置英国，以及额外的国际财团数据。参与者 共有 126 291 名年龄在 40 至 70 岁之间的英国成年人，被招募到英国生物银行。测量 表型结果是终生使用大麻（包括初次和持续使用大麻）、抑郁（包括单发和复发性抑郁）和自残。使用全基因组遗传数据，并在处理遗传数据时将评估中心、批次和前六个主要成分作为关键协变量包括在内。在英国生物银行中，使用大麻会增加患抑郁症的可能性 [比值比 (OR) = 1.64，95% 置信区间 (CI) = 1.59-1.70] 和自残（OR = 2.85，95% CI = 2.69 -3.01）。当考虑更严重的大麻使用和抑郁特征定义时，这种表型关联的强度会更强。使用联盟全基因组汇总统计数据，大麻使用与抑郁症之间存在显着的遗传相关性 [rg = 0.289，标准误 (SE) = 0.036]。大麻使用和抑郁的多基因风险评分解释了英国生物银行目标样本中大麻使用、抑郁和自我伤害的一小部分但显着的差异。然而，两样本孟德尔随机化分析并不显着。结论 大麻的使用似乎在表型和遗传上都与抑郁和自残有关。统计功效的限制意味着无法对这些特征之间的因果关系方向做出结论。然而，两样本孟德尔随机化分析并不显着。结论 大麻的使用似乎在表型和遗传上都与抑郁和自残有关。统计功效的限制意味着无法对这些特征之间的因果关系方向做出结论。然而，两样本孟德尔随机化分析并不显着。结论 大麻的使用似乎在表型和遗传上都与抑郁和自残有关。统计功效的限制意味着无法对这些特征之间的因果关系方向做出结论。