Interpretation of treating different diseases with the same method: a bidirectional Mendelian randomization study of the association between depression and insomnia

Objective: Mendelian randomization (MR) has been widely utilized for causal inference between diseases, and its implementation within the domain of traditional Chinese medicine (TCM) is considered feasible. Although previous clinical and epidemiological studies have demonstrated a close relationship between insomnia and depression, the inherent genetic factors underlying these associations are unclear. The aim of this study was to evaluate the causal relationship between depression and insomnia via bidirectional 2-sample MR and increase the understanding of the TCM theory of treating different diseases with the same method, particularly in the context of comorbid depression and insomnia. Methods: Genetic data related to depression and insomnia were extracted from published genome-wide association studies (GWAS) data sets. Single-nucleotide polymorphisms (SNPs) associated with depression and insomnia were used as instrumental variables to construct an “SNP-exposure-outcome” model. Bidirectional 2-sample MR analysis was conducted via inverse-variance weighted (IVW), weighted median, MR Egger regression, simple mode, and weighted mode methods. Furthermore, heterogeneity tests, pleiotropy analyses, and sensitivity analyses were performed. Results: The MR results revealed a causal relationship between depression and an increased risk of developing insomnia (IVW, OR=1.400, 95% CI: 1.246–1.573, P <0.001), and a causal relationship between insomnia and an increased risk of developing depression (IVW, OR=1.204, 95% CI: 1.144–1.266, P <0.001). Conclusions: There is a bidirectional causal relationship between depression and insomnia. These findings provide new theoretical support for the TCM approach of treating different diseases with the same method in the prevention and treatment of depression and insomnia and provide a scientific basis for the modernization of TCM.