Effects of Insomnia on Peptic Ulcer Disease Using Mendelian Randomization

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.

Potential genetic and epigenetic mechanisms in insomnia: A systematic review

“…In this framework, GWAS SNPs genetic pre‐disposition to insomnia were found to have a significant causal effect on the risk of some mental conditions such as major depression, bipolar disorder type II, schizophrenia, autism spectrum disorder, alcohol, nicotine and opioid use, attention‐deficit/hyperactivity disorder, anxiety and post‐traumatic stress disorder (PTSD), and suicidal behaviours with reverse causality observed for major depression, nicotine use, and PTSD only (Jansen, Dolinoy, et al, 2019, Jansen, Watanabe, et al, 2019; Gao et al, 2019; Song et al, 2020; Pasman et al, 2020; Lewis et al, 2020; Cai et al, 2021; Huang et al, 2021; Carpena et al, 2021; Watanabe et al, 2022; Sun et al, 2022; Baranova et al, 2022; Zhou et al, 2022; Nassan et al, 2022). Similarly, GWAS SNPs genetic pre‐disposition to insomnia were found to have a significant causal one‐way effect on the risk of some medical conditions including: coronavirus disease 2019 (COVID‐19) susceptibility (Peng et al, 2022), cognitive impairment, neurodegenerative conditions (Sun et al, 2020; Zhang et al, 2022), cardiovascular diseases (Jansen, Dolinoy, et al, 2019; Jansen, Watanabe, et al, 2019; Jia et al, 2022; Liu et al, 2021; Zheng et al, 2020), diabetes, cardio‐metabolic risks (Gao et al, 2020; Jansen, Dolinoy, et al, 2019; Jansen, Watanabe, et al, 2019; Liu et al, 2021; Liu et al, 2022), increasing the odds of reporting pain conditions (An et al, 2022; Broberg et al, 2021; Chu et al, 2021; Shu et al, 2022) and for other medical conditions (Bao et al, 2022; He et al, 2022; Huo et al, 2021; Zha et al, 2021).…”

Mendelian randomization indicates that atopic dermatitis contributes to the occurrence of diabetes

“…We extracted 21 SNPs with genome-wide significance ( P < 5 × 10 − 8 ) in the EAGLE study [ 27 ]. An SNP (rs12730935) was removed due to linkage disequilibrium (r 2 < 0.01, clump distance < 10,000 kb) [ 28 ] based on 1000 genomes European population [ 29 ]. SNPs with minor allele frequencies (MAF) < 0.01 also need to be excluded since they usually tend to have low confidence and no SNPs were excluded in this step.…”

Protective Effects of Circulating TIMP3 on Coronary Artery Disease and Myocardial Infarction: A Mendelian Randomization Study

“…First, we set a genome−wide significance at p < 5 × 10 −8 , leaving 33 SNPs that satisfied the first key assumption (relevance assumption). Then, we performed a clumping process (r 2 , 0.1; clumping window, 10,000 kb) [ 20 ] with reference to the 1000 genomes European panel [ 21 ] to avoid the influence of linkage disequilibrium. For the third key assumption (exclusion restriction assumption), we performed the MR Steiger filtering test to identify the SNPs suggestive of causality in the reverse direction [ 22 ] and remove these SNPs, if any ( Table S2 ).…”