The relationship between insomnia and multiple gastrointestinal disorders: a Mendelian randomization study.

BACKGROUND

Some observational studies have suggested an association between insomnia and the risk of certain gastrointestinal disorders, such as gastroesophageal reflux, irritable bowel syndrome and peptic ulcers. However, the direction and magnitude of the causal relationship are difficult to determine due to confounding and reverse causation. The aim of this study is to explore the causal association between insomnia and a variety of gastrointestinal disorders from genetic level using Mendelian randomization.

METHODS

We used a two-sample, two-way MR to analyze the link between insomnia and several gastrointestinal disorders (nine in total). Genetic variants used as instrumental variables were obtained from genome-wide association study (GWAS) data in the Open GWAS database. Causal effects were primarily estimated using inverse variance weighted (IVW), weighted median (WM) and MR-Egger. Horizontal pleiotropy was tested using MR-PRESSO and MR-Egger regression. Heterogeneity and sensitivity were assessed using Cochran's Q and leave-one-out.

RESULTS

The forward MR analysis demonstrated significant causal effects of insomnia on gastroesophageal reflux disease (GERD) (IVW: OR = 1.864, 95%CI: 1.16-2.98, P = 0.009) and irritable bowel syndrome(IBS) (IVW: OR = 2.401, 95%CI:1.06-5.44, P = 0.036; WM: OR = 3.381, 95%CI:1.12-10.22, P = 0.031). Conversely, reverse MR analyses indicated protective associations against insomnia development for chronic gastritis (IVW: OR = 0.98, 95%CI: 0.97-0.99, P = 0.027), while revealing risk-enhancing effects for acute gastritis (IVW: OR = 1.013, 95% CI: 1.006-1.019, P < 0.001). No causal associations were observed between insomnia and the remaining five gastrointestinal conditions.

CONCLUSIONS

Through bidirectional MR analysis of nine gastrointestinal disorders, we provide genetic evidence for causal effects of insomnia on four conditions: gastroesophageal reflux disease (GERD), irritable bowel syndrome (IBS), chronic gastritis, and acute gastritis.