ArticlePsychological medicine2022
Genetic correlation, pleiotropy, and causal associations between substance use and psychiatric disorder.
Article in Psychological medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 4 of them syntheses that pooled it.
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Who cites it
41 citing papers in PubMed, 4 syntheses or guidelines pooled it, 65 citations in OpenAlex.
- The impact of cannabis use on erectile dysfunction and sex hormones: a Mendelian randomization analysis.International journal of impotence research · 2025Pooled it
- Systematic Review and Meta-analysis of the Relationship Between Exposure to Parental Substance Use and Attention-Deficit/Hyperactivity Disorder in Children.Prevention science : the official journal of the Society for Prevention Research · 2024Pooled it
- Applications of Mendelian randomization in psychiatry: a comprehensive systematic review.Psychiatric genetics · 2022Pooled it
- Pairwise genetic meta-analyses between schizophrenia and substance dependence phenotypes reveals novel association signals with pharmacological significance.Translational psychiatry · 2022Pooled it
- Early-life tobacco exposure elevating childhood attention-deficit hyperactivity disorder risk: a two-sample Mendelian randomisation analysis.European archives of psychiatry and clinical neuroscience · 2026Article
- Genetic Pathways Point to the Biology Underlying the Association Between Cannabis Use Disorder and Psychosis.Biological psychiatry global open science · 2026Article
- Integrative analysis of single nucleotide polymorphism of PDE7B (rs2327669) with biopsychosocial and biochemical parameters in β-thalassemia major patients in Pakistani Cohort.Molecular biology reports · 2026Article
- Genetic liability to addiction underlies comorbid bipolar and substance use disorders.medRxiv : the preprint server for health sciences · 2026Article
- Genome-wide association studies of lifetime and frequency of cannabis use in 131,895 individuals.Molecular psychiatry · 2026Article
- Betel-quid Use Is Associated with Depression.International journal of medical sciences · 2026Article
- Utilising genomic association data for causal inference in anorexia nervosa.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Review
- Disentangling horizontal and vertical Pleiotropy in genetic correlation estimation: introducing the HVP model.Human genetics · 2025Article
- The causal effect of smoking on psychiatric disorders: an examination of brain volume as a potential pathway.Psychological medicine · 2025Article
- Disentangling the effects of nicotine versus non-nicotine constituents of tobacco smoke on major depressive disorder: A multivariable Mendelian randomisation study.Addiction (Abingdon, England) · 2025Article
- Heterogeneity analysis provides evidence for a genetically homogeneous subtype of bipolar-disorder.PloS one · 2025Article
- Psychological, social factors, and smoking behavior mediated the effects of cannabis use on personality disorders: A Mendelian randomization study.Frontiers in psychiatry · 2025Article
- Heterogeneity analysis provides evidence for a genetically homogeneous subtype of bipolar-disorder.ArXiv · 2024Article
- Genetic influences and causal pathways shared between cannabis use disorder and other substance use traits.Molecular psychiatry · 2024Article
- Genetic contribution to the comorbidity between attention-deficit/hyperactivity disorder and substance use disorders.Psychiatry research · 2024Article
- Genetic and shared environmental factors explain the association between adolescent polysubstance use and high school noncompletion.Psychology of addictive behaviors : journal of the Society of Psychologists in Addictive Behaviors · 2024Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundSubstance use occurs at a high rate in persons with a psychiatric disorder. Genetically informative studies have the potential to elucidate the etiology of these phenomena. Recent developments in genome-wide association studies (GWAS) allow new avenues of investigation.
methodUsing results of GWAS meta-analyses, we performed a factor analysis of the genetic correlation structure, a genome-wide search of shared loci, and causally informative tests for six substance use phenotypes (four smoking, one alcohol, and one cannabis use) and five psychiatric disorders (ADHD, anorexia, depression, bipolar disorder, and schizophrenia).
resultsTwo correlated externalizing and internalizing/psychosis factor were found, although model fit was beneath conventional standards. Of 458 loci reported in previous univariate GWAS of substance use and psychiatric disorders, about 50% (230 loci) were pleiotropic with additional 111 pleiotropic loci not reported from past GWAS. Of the 341 pleiotropic loci, 152 were associated with both substance use and psychiatric disorders, implicating neurodevelopment, cell morphogenesis, biological adhesion pathways, and enrichment in 13 different brain tissues. Seventy-five and 114 pleiotropic loci were specific to either psychiatric disorders or substance use phenotypes, implicating neuronal signaling pathway and clathrin-binding functions/structures, respectively. No consistent evidence for phenotypic causation was found across different Mendelian randomization methods.
conclusionsGenetic etiology of substance use and psychiatric disorders is highly pleiotropic and involves shared neurodevelopmental path, neurotransmission, and intracellular trafficking. In aggregate, the patterns are not consistent with vertical pleiotropy, more likely reflecting horizontal pleiotropy or more complex forms of phenotypic causation.
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