Causal Relationships between Overall and Abdominal Obesity and Varicose Veins: A Two- Sample Mendelian Randomization Study

Abstract Purpose The association between obesity and varicose veins is recognized; however, the specific causal links between different types of obesity and varicose veins remain unclear. Our study explores the causal effects of general and abdominal obesity on varicose veins through Mendelian randomization. Methods We conducted univariable (UVMR) and multivariable (MVMR) Mendelian randomization, using body mass index (BMI) and waist circumference (WC) as proxies for general and abdominal obesity, respectively. The Mendelian randomization analysis utilized genome-wide association study (GWAS) data from the UK Biobank (UKB) and FinnGen. Instrumental variables were identified from SNP data, requiring strong association (P < 5e–8) and independence (r2 < 0.001). Inverse variance weighted (IVW) analysis was the primary method for causal inference. Extensive sensitivity analyses were also performed to confirm the validity of our results. Results UVMR showed a causal link between higher BMI and increased incidence of varicose veins (OR = 1.304, CI = 1.209–1.407, P = 6.778e-12), while WC was similarly associated (OR = 1.478, CI = 1.335–1.636, P = 5.092e-14). In MVMR analyses controlling for BMI, WC was found to have a direct causal effect on varicose veins (OR = 1.654, 95% CI: 1.066–2.568, P = 0.0248). After adjusting for WC, the data did not support a direct causal link between BMI and varicose veins (OR = 0.899, 95% CI: 0.632–1.277, P = 0.0551). Conclusion This study suggests that WC might be a more precise indicator of the relationship between obesity and varicose veins compared to BMI.