Causal associations between lifestyle factors and hemorrhoidal disease: Insights from Mendelian randomization...

Prior investigations have indicated an association between sedentary and physically active behaviors, tobacco and alcohol intake behaviors, and hemorrhoidal disease (HD). Yet, the causal relationship between these factors and HD remains unclear and is a topic of debate. The data from the genome-wide association study were selected as the exposures (sedentary behavior, physical activity behavior, and tobacco and alcohol intake behavior) and the outcome (HD). We employed a range of Mendelian randomization (MR) analysis methods for causal estimation. The primary analysis method was the inverse variance weighted random effect model (IVW[RE]), with the MR-Egger, weighted median estimator, MR-pleiotropy residual sum and outlier (MR-PRESSO), MR-Radial, and MR-LAP methods serving as auxiliary and supplementary. Additionally, secondary MR analyses were conducted by identifying and removing outlier single nucleotide polymorphisms through MR-Radial. A series of sensitivity analyses were performed to ascertain the reliability and robustness of the results. Among the MR analysis results, the IVW(RE) results for Leisure screen time's analysis with HD showed an odds ratio (OR) of 1.052 (95% confidence interval [CI]: 1.001-1.106, P: .047). After the removal of outliers, the IVW(RE) OR was 1.055 (95% CI: 1.015-1.096, P: .006). For the smoking initiation analysis with HD, the P difference in the MR-LAP results was 0.031. The MR-LAP corrected IVW results were deemed to be more plausible, with an OR of 1.058 (95% CI: 1.020-1.096, P: .002). After the removal of outliers, the IVW(RE) yielded an OR of 1.066 (95% CI: 1.007-1.129, P: .029). In the initial analysis of moderate-to-vigorous intensity physical activity during leisure time with HD, weighted median estimator yielded a negative correlation (OR: 0.856, 95% CI: 0.750-0.978, P: .022). Following the removal of outliers, the IVW(RE) results indicated a negative correlation (OR: 0.900, 95% CI: 0.814-0.995, P: .039). For smoking cessation analysis with HD, P difference was found to be statistically significant (.034) in the MR-LAP results. The corrected IVW results yielded an OR of 0.951 (95% CI: 0.907-0.997, P: .035). The secondary analysis yielded an OR of 0.901 (95% CI: 0.812-1.000, P: .05). However, no notable correlation was identified between alcohol consumption and HD in the conducted analyses. The results indicate that sedentary and smoking behaviors are risk factors, whereas physical active and smoking cessation are possible protective factors. The study provides evidence for further research into the etiology of HD and enables the development of prevention strategies.