CAUSAL RELATIONSHIP BETWEEN SUBSTANCE USE AND INSOMNIA: A BIDIRECTIONAL MENDELIAN RANDOMIZATION STUDY

Abstract Background Insomnia is a significant factor that affects both physical and mental health and may increase the risk of various mental disorders, causing a considerable burden on mental health. Substance use, particularly tobacco and alcohol use, is a significant health issue affecting the Chinese population. Previous studies have suggested a correlation between substance use, such as tobacco and alcohol, and the occurrence of insomnia, and insomnia may further aggravate substance use problems. However, the causal relationship between the two is still unclear. Aims & Objectives This study aimed to use a bidirectional Mendelian randomization approach to explore the causal relationship between substance use and insomnia. Method The Mendelian randomization (MR) method used genome-wide association study (GWAS) summary data to study the causal relationship between exposure and outcome. Bidirectional MR tested the bidirectional effects of the two factors and determined the bidirectional causal relationship between the two factors. This study used GWAS data on alcohol addiction (N = 6514), weekly alcohol consumption (N = 335394), smoking initiation (N = 607291), daily smoking quantity (N = 249752), and two insomnia traits (N = 462341; N = 336965) to conduct bidirectional MR analysis and confirmed the robustness of the analysis using sensitivity analysis. Results The bidirectional MR results indicated that weekly alcohol consumption (IVW: P = 0.017, b = 0.063; Weighted median: P = 0.025, b = 0.048) and smoking initiation (IVW: P = 0.008, b = 0.036; Weighted median: P = 0.04, b = 0.023) had promoting effects on insomnia. However, although IVW suggested that insomnia had an effect on alcohol addiction (P = 0.036) and daily smoking quantity (P = 0.016), sensitivity analysis using methods such as Weighted median and Weighted mode did not support this. Discussion & Conclusion This study, through bidirectional MR analysis, found that tobacco use and alcohol consumption have a promoting effect on insomnia, which is consistent with previous reports. However, this study's results do not support the speculation that insomnia itself promotes alcohol and tobacco use. Insomnia caused by alcohol and tobacco use may be related to the neural excitability and awakening function abnormalities caused by substance use, and patients with insomnia may be less likely to seek relief through tobacco and alcohol. This study reveals the potential causal relationship between substance use and insomnia through Mendelian randomization analysis based on large-scale GWAS data, providing new evidence for clinical diagnosis and treatment. Future large-scale cohort studies are needed to further explore the causal relationship between substance use and insomnia.