Causal Effects of Metabolic Syndrome on Gastric Disorders: Univariable and Multivariable Mendelian Randomization

Metabolic syndrome (MetS) has been associated with various gastrointestinal disorders, but the causal relationships between MetS components and gastric disorders remain unclear. Previous observational studies are limited by confounding factors and reverse causation.

This study aimed to investigate the causal effects of MetS components, including fasting blood glucose (FBG), high-density lipoprotein cholesterol (HDL-C), triglycerides (TGs), waist circumference (WC), and hypertension, on the risks of chronic gastritis, benign gastric tumors, and gastric cancer using mendelian randomization (MR) analyses.

Univariable 2-sample mendelian randomization (TSMR) and multivariable mendelian randomization (MVMR) analyses were employed to evaluate the independent and combined effects of MetS components on gastric disorders. The primary MR method used was the random effects inverse-variance weighted (IVW) approach.

Univariable TSMR analysis identified statistically significant associations between elevated TGs (odds ratio [OR] = 1.223, 95% CI, 1.011-1.480; P = .0386) and reduced HDL-C (OR = 0.833, 95% CI, 0.701-0.989; P = .037) with an increased risk of benign gastric tumors. However, these associations were not confirmed by MVMR for TGs (OR = 1.187, 95% CI, 0.891-1.581; P = .2408) or HDL-C (OR = 0.989, 95% CI, 0.758-1.289; P = .932). Both TSMR (OR = 0.585, 95% CI, 0.411-0.831; P = .003) and MVMR (OR = 0.558, 95% CI, 0.334-0.930; P = .025) indicated that hypertension is associated with a reduced risk of gastric cancer. No statistically significant associations were found for other MetS components and gastric disorders.

The findings suggest that specific MetS components, such as TGs and HDL-C, may affect the risk of benign gastric tumors, while hypertension might reduce the risk of gastric cancer. This study highlights the need for further research to understand the underlying mechanisms and potential indirect effects between MetS components and gastric disorders.