April 28, 2025Diabetology & Metabolic SyndromeOpen Access

Analysis of causal effects on metabolic syndrome and inflammatory bowel disease: a Mendelian randomization study

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Why the study?

Epidemiological studies had not yet determined whether metabolic syndrome and inflammatory bowel disease are causally related.

Do genetic variants associated with metabolic syndrome components affect the risk of inflammatory bowel disease?

Structured PICO

Do genetic variants associated with metabolic syndrome components affect the risk of inflammatory bowel disease?

Population

Publicly available genome-wide association study (GWAS) data from the IEU OpenGWAS project and IIBDGC (International Inflammatory Bowel Disease Genetic Consortium) for metabolic syndrome and inflammatory bowel disease

Intervention

Genetic variants associated with metabolic syndrome components (fasting blood glucose, HDL-C, triglyceride, waist circumference, and hypertension)

Outcome

Risk of Inflammatory Bowel Disease (IBD) and its subtypes (e.g., Crohn's disease)

Mendelian randomization suggests that certain metabolic syndrome components, such as hypertension and fasting blood glucose, may have causal effects on the risk of inflammatory bowel disease and Crohn's disease.

Limitations

Confounding factors cannot be completely ruled out

Implication

No causal MetS-IBD link supported; leaves open shared risk factors or confounders for targeted prospective studies.

Abstract

BACKGROUND: Metabolic syndrome (MetS) is a conglomerate of metabolic abnormalities including hypertension, obesity, hyperglycemia, hypertriglyceridemia, and low levels of high-density lipoprotein cholesterol (HDL-C). The relationship between MetS and Inflammatory Bowel Disease (IBD) has received a lot of attention lately. Epidemiological investigation has yet to determine if the two illnesses are causally related. To investigate the causal link between IBD and MetS levels, we screened publically available genome-wide association study (GWAS) data using Mendelian randomization (MR) analysis. The study aimed to comprehensively analyze the causal association of each component of MetS, including fasting blood glucose(FBG), HDL-C, triglyceride(TG), waist circumference(WC), and hypertension, on the risk of IBD and its subtypes via univariate, two-way, and multivariate MR (MVMR) methods. METHODS: We selected independent genetic variants of MetS and IBD as instrumental variables (IVs) from published data from the IEU OpenGWAS project and IIBDGC (International Inflammatory Bowel Disease Genetic Consortium), used MR to infer potential causal effects between them, and used a variety of methods (random effect inverse variance weighting (IVW), weighted median, MR-Egger regression, etc.) to ensure the robustness of causal effects. RESULTS: Univariate two-sample MR (TSMR) revealed that WC was significantly linked to the risk of Crohn's disease (CD) (OR = 1.659; 95% CI: 1.144-2.405; p = 0.008) and IBD (OR = 1.383; 95% CI: 1.050-1.822; p = 0.021). However, MVMR did not support this finding. In MVMR analysis, hypertension was predicted to be positively associated with the risk of IBD (OR = 2.322516, 95% CI: 1.097713-4.91392, p = 0.0275365), whereas FBG was confirmed to reduce the risk of CD in MVMR studies (OR = 0.4346427, 95% CI: 0.2685399-0.7034868, p = 0.0006948939). Other elements of the MetS did not significantly correlate with IBD. CONCLUSION: Although confounding factors cannot be completely ruled out, certain metabolic components, such as WC, may impact the risk of IBD. In addition to highlighting the need for more research to understand the underlying mechanisms and potential indirect effects between MetS components and IBD, this research offers insight into therapeutic treatment decisions for patients with IBD and MetS.