Alleviating insomnia should decrease the risk of irritable bowel syndrome: Evidence from Mendelian randomization.

Associations have been reported between sleep and irritable bowel syndrome (IBS). However, whether there exists a causation between them is still unknown. We employed the Mendelian randomization (MR) design to explore the causal relationship between sleep and IBS. All genetic associations with sleep-related traits reached genome-wide significance (-value < 5 × 10-8). The genetic associations with IBS were obtained from two independent large genome-wide association studies (GWAS), where non-FinnGen GWAS was in the discovery stage and FinnGen GWAS was in the validation stage. Primarily, the inverse-variance weighted method was employed to estimate the causal effects, and a meta-analysis was performed to combine the MR estimates. In the discovery, we observed that genetic liability to the "morning" chronotype could lower the risk of IBS [OR = 0.81 (0.76, 0.86)]. Also, the genetic liability to insomnia can increase the risk of IBS [OR = 2.86 (1.94, 4.23)] and such causation was supported by short sleep duration. In the validation stage, only insomnia displayed statistical significance [OR = 2.22 (1.09, 4.51)]. The meta-analysis suggested two genetically-determined sleep exposures can increase the risk of IBS, including insomnia [OR = 2.70 (1.92, 3.80)] and short sleep duration [OR = 2.46 (1.25, 4.86)]. Furthermore, the multivariable MR analysis suggested insomnia is an independent risk factor for IBS after adjusting for chronotype [OR = 2.32 (1.57, 3.43)] and short sleep duration [OR = 1.45 (1.13, 1.85)]. IBS cannot increase the risk of insomnia in the reverse MR analysis. Genetic susceptibility to insomnia can increase the risk of IBS, and improving sleep quality, especially targeting insomnia, can help to prevent IBS.