INTRODUCTION: Secondhand smoke (SHS) may exacerbate the global disease burden, particularly in workplace settings. Observational studies have implicated SHS as a risk factor for various non-malignant digestive system diseases (NMDSD), yet establishing a causal relationship remains challenging. Therefore, we conducted a Mendelian randomization (MR) study to explore whether workplace exposure to SHS is associated with NMDSD. METHODS: This study utilized a secondary dataset analysis based on Genome-Wide association study (GWAS) summary data. Genetic variants associated with exposure to SHS in the workplace were used as instrumental variables. Genome-wide association study (GWAS) summary data for SHS were obtained from the UK Biobank. GWAS summary data for NMDSD were sourced from the FinnGen study, the International Inflammatory Bowel Disease Genetics Consortium (IIBDGC), and a large-scale study conducted in Japan. We employed inverse variance-weighted (IVW), MR-Egger, and weighted median methods for MR analysis. Additionally, sensitivity analyses were conducted to ensure the robustness of our findings. RESULTS: According to the IVW model, SHS in the workplace was positively associated with ulcerative colitis (UC) (OR=2.03
95% CI: 1.03-4.05
p=0.04). There was no evidence of horizontal pleiotropy biasing causality (p>
0.05), and leave-one-out analysis confirmed the stability and robustness of this association. CONCLUSIONS: Our study identifies an association between regular exposure to SHS in the workplace and an increased risk of ulcerative colitis. However, the potential influence of active smoking or exposure to SHS from other sources cannot be excluded. Further research is needed to confirm these findings.