Abstract
Objectives Observational studies indicate that insomnia may increase risk of peptic ulcer disease (PUD). Our purpose is to clarify the possible causal relationship between insomnia and PUD by Mendelian randomization analyses. Methods We carried out analyses using summary statistics data for genetic variants reported from a GWAS of insomnia (N = up to 1,331,010 individuals) and from a GWAS of PUD (N = up to 456,327 individuals). Three Mendelian randomization approaches were used to explore whether insomnia might play a causal role in PUD, and pathway and functional enrichment analyses were conducted to anticipate the underlying mechanisms. Results Conventional Mendelian randomization analysis showed clear causality between insomnia and PUD; 1 SD increased insomnia incident was related to a 19% higher risk of PUD (P = 6.69 × 10−16; OR, 1.19 (95% CI, 1.14-1.24)). The associations between insomnia and PUD were consistent in the other two analyses performed using the weighted median method (P = 7.75 × 10−7; OR, 1.16 (95% CI, 1.09-1.23)) and MR-Egger regression (P = 5.00 × 10−3; OR, 1.27 (95% CI, 1.07-1.50)). Moreover, no evidence indicated a reverse causality between PUD events and insomnia symptoms. Pathway and functional enrichment analyses indicated that the mechanisms of insomnia effect on PUD may be through various ways, such as the immune system and oxidative stress. Conclusions This Mendelian randomization study suggests insomnia as a causal risk factor for PUD. The potential mechanisms included may be immune and oxidative stress. These findings indicate that improving sleep quality could have substantial health benefits.
Highlights
Insomnia is a common mental disorder; it is by far the most common sleep disorder in medical practice
For our secondary phase analysis, in order to make our sensitivity analysis to achieve sufficient statistical power, another larger set of SNPs was used in our main analysis, which was retrieved from a recent genome-wide association studies (GWASs) for insomnia involving 1,331,010 European people [12]
248 independent SNPs were significantly associated with insomnia (P < 5 × 10−8; r2 < 0:1). 242 of them were included in the Peptic ulcer disease (PUD) GWAS dataset and were chosen for the MR analysis
Summary
Insomnia is a common mental disorder; it is by far the most common sleep disorder in medical practice. About 30% of the common population report symptoms of insomnia [1]. Insomnia is considered as a key factor referring to the occurrence and progress of chronic inflammatory diseases; it is closely associated with gastrointestinal symptoms, high blood pressure, asthma, systemic lupus erythematosus, autonomic nervous system dysfunction, impaired blood sugar control, and increased inflammation [2]. Peptic ulcer disease (PUD) is a common gastrointestinal disease involving rupture (ulceration) of the alimentary canal mucosa, mainly occurring in the gastric area and duodenum. Epidemiology shows that the annual incidence of PUD is 0.1-0.3%, and the lifetime prevalence in the general population is about 5-10% [3]. More than 4 million people suffer from the disease each year, resulting in high medical
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