Genetic liability to obesity and peptic ulcer disease: a Mendelian randomization study

Abstract

Background Epidemiological evidence relating obesity to peptic ulcer disease (PUD) has been mixed. Here we sought to determine the causality in the association of obesity with PUD risk using the Mendelian randomization (MR) approach. Methods This study was based on summary-level data for body mass index (BMI), waist-to-hip ratio (WHR), and PUD derived from large genome-wide association studies (GWASs). Single nucleotide polymorphisms significantly associated with BMI and WHR (P < 5 × 10–8) were leveraged as instrumental variables. Causal estimates were pooled using several meta-analysis methods. In addition, multivariable MR was employed to account for covariation between BMI and WHR, as well as to explore potential mediators. Results Genetically predicted higher BMI has a causal effect on PUD, with an OR of 1.34 per SD increase in BMI (~ 4.8 kg/m2) (P = 9.72 × 10–16). Likewise, there was a 35% higher risk of PUD (P = 2.35 × 10–10) for each SD increase in WHR (0.09 ratio). Complementary analyses returned consistent results. Multivariable MR demonstrated that adjustment for WHR largely attenuated the BMI-PUD association. However, the causal association of WHR with PUD risk survived adjustment for BMI. Both the associations remained robust upon adjustment for several traditional risk factors. Replication analyses using different instrumental variants further strengthened the causal inference. Besides, we found no evidence for the causal association in the reverse analyses from PUD to BMI/WHR. Conclusions This MR study revealed that obesity (notably abdominal obesity) is causally associated with higher PUD risk. Programs aimed at weight loss may represent therapeutic opportunities for PUD.

Causal relationships of Helicobacter pylori and related gastrointestinal diseases on Type 2 diabetes: Univariable and Multivariable Mendelian randomization

“…In our study, we carried out a Mendelian randomization study of the three diseases most likely to be induced by H. pylori with T2DM, and the results showed that gastric cancer was not causally related to T2DM, while gastroduodenal ulcer and chronic gastritis were associated with the development of T2DM, and in order to further explore the mechanism of the occurrence of this causality, we compared the two diseases with the T2DM development, respectively. Mendelian analysis of obesity, HbA1c and blood glucose levels, respectively, which showed that gastroduodenal ulcer was a risk factor for increased risk of obesity, so we hypothesized that obesity might be a mediator between gastroduodenal ulcer and T2DM, and then we carried out the validation, and the result was in line with our speculation that gastroduodenal ulcer mediated T2DM through obesity, which was in line with the results of previous results of a Mendelian study on the association between peptic ulcer and obesity [38], therefore, obese patients with gastroduodenal ulcer should be carefully managed to prevent T2DM.…”

Stroke and the risk of gastrointestinal disorders: A Mendelian randomization study

“…It is reported that obesity, smoking, anticoagulant, and other risk factors are often related to gastrointestinal diseases ( 39 – 41 ). The GWAS of GERD and PUD found genetic overlapping with the identified aforementioned hazardous factors ( 42 , 43 ). We cannot rule out that SNP affects the outcome through other related variables.…”

Evidence for causal effects of polycystic ovary syndrome on oxidative stress: a two-sample mendelian randomisation study

“…Mendelian randomisation (MR) is an instrumental variable (IV) analysis that detects and quantifies causality using genetic variation as an IV [ 23 ]. Because of its ability to overcome potential confounding factors and reverse causality, MR has been increasingly used in observational studies in recent years [ 24 – 26 ]. Therefore, this study aimed to clarify the causal association between PCOS, its characteristics, and OS using a two-sample MR study.…”