Behavioural Science Institute, Radboud University Nijmegen, the Netherlands.
Department of Psychiatry, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
Drug Alcohol Depend. 2020 Sep 1;214:108151. doi: 10.1016/j.drugalcdep.2020.108151. Epub 2020 Jul 2.
Poor sleep quality and insomnia have been associated with the use of tobacco, alcohol, and cannabis, but it is unclear if there is a causal link. In this Mendelian Randomization (MR) study we examine if insomnia causes substance use and/or if substance use causes insomnia.
MR uses summary effect estimates from a genome-wide association study (GWAS) to create a genetic instrumental variable for a proposed 'exposure' variable and then identifies that same genetic instrument in an 'outcome' GWAS. Using GWASs of insomnia, smoking (initiation, heaviness, cessation), alcohol use (drinks per week, dependence), and cannabis initiation, bi-directional causal effects were tested. Multiple sensitivity analyses were applied to assess the robustness of the findings.
There was strong evidence for positive causal effects of liability to insomnia on all substance use phenotypes (smoking traits, alcohol dependence, cannabis initiation), except alcohol per week. In the other direction, there was strong evidence that smoking initiation increased insomnia risk (smoking heaviness and cessation could not be tested as exposures). We found no evidence that alcohol use per week, alcohol dependence, or cannabis initiation causally affect insomnia risk.
There were unidirectional effects of liability to insomnia on alcohol dependence and cannabis initiation, and bidirectional effects between liability to insomnia and smoking measures. Bidirectional effects between smoking and insomnia might give rise to a vicious circle. Future research should investigate if interventions aimed at insomnia are beneficial for substance use treatment.
睡眠质量差和失眠与吸烟、饮酒和使用大麻有关，但目前尚不清楚是否存在因果关系。在这项孟德尔随机化（MR）研究中，我们研究了失眠是否会导致物质使用，或者物质使用是否会导致失眠。
MR 使用全基因组关联研究（GWAS）的汇总效应估计值来创建拟议“暴露”变量的遗传工具变量，然后在“结果”GWAS 中识别出相同的遗传工具。使用失眠、吸烟（开始、吸烟量、戒烟）、饮酒（每周饮酒量、依赖）和大麻开始的 GWAS，测试了双向因果效应。应用了多种敏感性分析来评估研究结果的稳健性。
有强有力的证据表明，易患失眠与所有物质使用表型（吸烟特征、酒精依赖、大麻开始）之间存在正向因果关系，除了每周饮酒量。在另一个方向上，有强有力的证据表明，吸烟开始增加了失眠的风险（无法测试吸烟量和戒烟作为暴露）。我们没有发现每周饮酒量、酒精依赖或大麻开始会导致失眠风险的证据。
易患失眠对酒精依赖和大麻开始有单向影响，而失眠和吸烟之间存在双向影响。吸烟和失眠之间的双向影响可能会导致恶性循环。未来的研究应调查针对失眠的干预措施是否对物质使用治疗有益。
