Causal association between metabolic syndrome and cholelithiasis: a Mendelian randomization study

Abstract

BackgroundMetabolic syndrome (MetS) has been associated with digestive system diseases, and recent observational studies have suggested an association between MetS and cholelithiasis. However, the causal relationship between them remains unclear. This study aimed to assess the causal effect of MetS on cholelithiasis using Mendelian randomization (MR) analysis.MethodsSingle nucleotide polymorphisms (SNPs) of MetS and its components were extracted from the public genetic variation summary database. The inverse variance weighting method (IVW), weighted median method, and MR-Egger regression were used to evaluate the causal relationship. A sensitivity analysis was performed to ensure the stability of the results.ResultsIVW showed that MetS increased the risk of cholelithiasis (OR = 1.28, 95% CI = 1.13–1.46, P = 9.70E−05), and the weighted median method had the same result (OR = 1.49, 95% CI = 1.22–1.83, P = 5.68E−05). In exploring the causal relationship between MetS components and cholelithiasis, waist circumference (WC) was significantly associated with cholelithiasis. IVW analysis (OR = 1.48, 95% CI = 1.34–1.65, P = 1.15E−13), MR-Egger regression (OR = 1.62, 95% CI = 1.15–2.28, P = 0.007), and weighted median (OR = 1.73, 95% CI = 1.47–2.04, P = 1.62E−11) all found the same results.ConclusionOur study indicated that MetS increases the incidence of cholelithiasis, especially in MetS patients with abdominal obesity. Control and treatment of MetS can effectively reduce the risk of gallstone formation.

Causality between cholelithiasis and ileus: a two-sample Mendelian randomization study

“…The Cochran Q test served to assess heterogeneity, and a subsequent sensitivity analysis was conducted to validate the robustness of the results 8 . Mendelian randomization analysis proves instrumental in elucidating causal relationships by effectively controlling for confounding variables 2 . The instrumental variables in MR Analysis must adhere to three foundational assumptions: (1) a strong correlation between the selected genetic tools and exposure variables 2 ; (2) an absence of association between genetic tools and any confounding factors 2 ; (3) genetic tools having no shared causation with the outcome, with only exposure variables in uencing the outcome 2 .…”

“…Each method was applied separately to estimate the causal relationship between cholelithiasis and ileus. The MR-Egger and weighted median techniques were incorporated to complement the IVW estimates, as these approaches yield more resilient estimates across a broader spectrum of scenarios, albeit with slightly reduced e cacy 2 . Please refer to Tables 5 and 6 for a detailed presentation of the ndings.…”

“…Mendelian randomization (MR) analysis, employing single nucleotide polymorphisms (SNPs) as instrumental variables (IV) to mitigate the in uence of confounding variables, has become a widely adopted approach for discerning causal relationships between risk factors and diseases 2 . The MR Analysis in this study utilized aggregated data from genome-wide association studies (GWAS), encompassing a myriad of genetic variants.…”

“…Among these individuals, up to 20 percent may encounter complications such as cholecystitis, cholangitis, pancreatitis, gallbladder perforation, and sepsis. Notably, cholelithiasis leads to a substantially elevated rate of hospitalization compared to other gastrointestinal maladies 1 , thereby not only escalating the nancial burden on healthcare but also posing a signi cant threat to individual life 2 .…”

“…This discrepancy constitutes the primary limitation of our study. Secondarily, the study cohort primarily comprised individuals of European descent, thereby constraining the generalizability of the ndings to other ethnic groups with disparate lifestyles-a secondary limitation in this study2 . Furthermore, the utilization of GWAS aggregate-level statistics precluded the exploration of strati cation effects based on variables such as sex, age, or other factors.…”