Divergent associations between adiposity and hernia subtypes in European populations: A Mendelian randomization study

Obesity is a suspected risk factor for hernia, but observational studies are susceptible to confounding and reverse causation. We aimed to investigate the causal effects of general and central adiposity on 5 hernia subtypes using Mendelian randomization (MR). Two-sample MR analyses were conducted using genetic instruments for 7 adiposity traits from the UK Biobank and hernia outcome data (diaphragmatic, femoral, inguinal, umbilical, and ventral hernias) from the Finn Gen consortium. The inverse-variance weighted method was the primary analysis, complemented by MR Egger and weighted median methods. Sensitivity analyses assessed heterogeneity, horizontal pleiotropy, and directionality. Outliers were removed in a confirmatory MR analysis. All P values were adjusted using the Benjamini-Hochberg (BH) method. Genetically predicted adiposity was associated with a decreased risk of inguinal hernia (e.g., body mass index [BMI] odds ratio [OR]: 0.84, 95% confidence interval [CI]: 0.76-0.92, PBH <.001) but an increased risk of umbilical hernia (BMI OR: 1.39, 95% CI: 1.18-1.63, PBH <.001) and ventral hernia (BMI OR: 1.93, 95% CI: 1.65-2.26, PBH <.001). These effects were consistent across adiposity measures. No significant causal effects were found for diaphragmatic or femoral hernias. Sensitivity analyses confirmed the robustness of findings, with no horizontal pleiotropy and valid causal direction. This MR study suggests that genetically predicted adiposity has divergent potential causal associations with hernia subtypes, protecting against inguinal hernia while increasing the risk of umbilical and ventral hernias. These findings, though limited to European populations and subject to the assumptions of MR, have implications for clinical risk stratification and weight management counseling.