Association between metabolic syndrome and inflammatory bowel disease: a bidirectional two-sample Mendelian...

Epidemiological studies have revealed parallel increases in the incidences of metabolic syndrome (MetS) and inflammatory bowel disease (IBD). Clinical observational studies have shown an association between MetS and a poor prognosis of IBD. However, the causal relationship between MetS and IBD remains unclear. This study used bidirectional two-sample Mendelian randomization to investigate potential causal links between MetS and IBD, including ulcerative colitis (UC) and Crohn's disease (CD).

Genetic associations of MetS and its components with IBD were sourced from public databases of European populations. Inverse variance weighting was conducted, with weighted median, Mendelian randomization-Egger (MR-Egger), and Mendelian randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) methods used as sensitivity analyses. This process was repeated in the opposite direction.

The inverse variance weighted (IVW) method showed that genetic prediction of MetS may be a potential risk factor for CD (OR = 1.34, 95% CI: 1.009-1.779; p = 0.043). In further estimating the different components of MetS, it was found that waist circumference may increase the risk of CD (OR = 1.33, 95% CI: 1.05-1.684; p = 0.018) and hypertension may increase the risk of UC (OR = 1.61, 95% CI: 1.084-2.39; p = 0.018). Reverse analysis showed that IBD may increase triglyceride levels (OR = 1.019, 95% CI: 1.000-1.038; p = 0.049).

This MR analysis showed a causal relationship between genetically predicted MetS and CD, and genetically predicted hypertension and UC. Therefore, these patients need to be closely monitored clinically for the risk of CD/UC comorbidities. In patients with IBD, close monitoring of MetS-associated cardiovascular risk is required.