Association between inflammatory bowel disease and osteoporosis in European and East Asian populations: exploring causality, mediation by nutritional status, and shared genetic architecture.

Background: While previous research has established an association between inflammatory bowel disease (IBD) and osteoporosis (OP), the nature of this association in different populations remains unclear. Objective: Our study used linkage disequilibrium scores(LDSC) regression analysis and Mendelian randomization(MR) to assess the genetic correlation and causal relationship between IBD and OP in European and East Asian populations. Methods: We performed separate genetic correlation and causal analyses for IBD and OP in European and East Asian populations, used the product of coefficients method to estimate the mediating effect of nutritional status on the causal relationship, and used multi-trait analysis to explore the biological mechanisms underlying the IBD-nutrition-OP causal pathway. Results: Our analysis revealed a significant genetic correlation and causal relationship between IBD and OP in the European population. Conversely, no such correlation or causal relationship was observed in the East Asian population. Mediation analysis revealed a significant mediating effect of nutritional status on the causal pathway between IBD and OP in the European population. Multi-trait analysis of the IBD-nutrition-OP causal pathway identified MFAP2, ATP13A2, SERPINA1, FTO and VCAN as deleterious variants. Conclusion: Our findings establish a genetic correlation and causal relationship between IBD and OP in the European population, with nutritional status playing a crucial mediating role.