关键词:

失眠, 便秘, 孟德尔随机化, 因果关系, 遗传流行病学

Abstract:

Objective　To investigate the causal relationship between insomnia and constipation using the bidirectional Mendelian randomization (MR) approach. Methods　The bidirectional MR analysis was conducted. The data from the large-scale genome-wide association study (GWAS) database of the IEU Open GWAS project was extracted from its establishment to July 2024. This encompassed the data on insomnia (4 462 341 cases) and constipation (411 623 cases). The instrumental variables (IVs) highly associated with insomnia and constipation were selected based on association analyses, after addressing linkage disequilibrium, and removing weak instruments. The inverse variance-weighted (IVW) method was the primary analytical technique, and supplemented by MR-Egger regression, the weighted median approach, and simple mode analysis to evaluate the causal effects between the two traits. Additionally, the heterogeneity and pleiotropy of the IVs were assessed with the IVW and MR-Egger's Cochran Q test for heterogeneity, and with MR-Egger regression intercept and MR-PRESSO for pleiotropy examination. The leave-one-out sensitivity analysis was employed to assess the robustness of the results. Results　Under the support of IVs conforming to MR assumptions, the IVW analysis indicated that insomnia increases the risk of constipation (OR=1.684, 95%CI 1.107-2.560, P=0.015); on the other hand, the causal effect of constipation on insomnia was not statistically significant (P>0.05). The results suggest that insomnia may be a risk factor for constipation. Conclusions　Insomnia may increase the risk of constipation. Conversely, no causal association is found for constipation leading to insomnia.

Key words:

Insomnia, Constipation, Mendelian randomization, Causal relationship, Genetic epidemiology