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.
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.
Authors: Jonathan D Schaefer; Nayla R Hamdi; Stephen M Malone; Scott Vrieze; Sylia Wilson; Matt McGue; William G Iacono Journal: Proc Natl Acad Sci U S A Date: 2021-04-06 Impact factor: 11.205
Authors: Courtney R Quick; Kevin P Conway; Joel Swendsen; Emma K Stapp; Lihong Cui; Kathleen R Merikangas Journal: JAMA Psychiatry Date: 2022-07-01 Impact factor: 25.911
Authors: Kai Xiang Lim; Frühling Rijsdijk; Saskia P Hagenaars; Adam Socrates; Shing Wan Choi; Jonathan R I Coleman; Kylie P Glanville; Cathryn M Lewis; Jean-Baptiste Pingault Journal: PLoS Med Date: 2020-06-01 Impact factor: 11.069
Authors: Catherine A Dennen; Kenneth Blum; Abdalla Bowirrat; Jag Khalsa; Panayotis K Thanos; David Baron; Rajendra D Badgaiyan; Ashim Gupta; Eric R Braverman; Mark S Gold Journal: Epigenomes Date: 2022-08-26
Authors: Kenneth Blum; Shan Kazmi; Edward J Modestino; Bill William Downs; Debasis Bagchi; David Baron; Thomas McLaughlin; Richard Green; Rehan Jalali; Panayotis K Thanos; Igor Elman; Rajendra D Badgaiyan; Abdalla Bowirrat; Mark S Gold Journal: J Pers Med Date: 2021-03-16
Authors: Jorien L Treur; Marcus R Munafò; Emma Logtenberg; Reinout W Wiers; Karin J H Verweij Journal: Psychol Med Date: 2021-05-25 Impact factor: 7.723