No genetic causal association between iron status and osteoporosis: A two-sample Mendelian randomization.

Objective: To explore the genetic causal association between osteoporosis (OP) and iron status through Mendelian randomization (MR). Methods: Publicly available genome-wide association study (GWAS) summary data were used for MR analysis with four iron status-related indicators (ferritin, iron, total iron binding capacity, and transferrin saturation) as exposures and three different types of OP (OP, OP with pathological fracture, and postmenopausal OP with pathological fracture) as outcomes. The inverse-variance weighted (IVW) method was used to analyze the genetic causal association between the four indicators of iron status and OP. The heterogeneity of MR results was determined using IVW and MR-Egger methods. The pleiotropy of MR results was determined using MR-Egger regression. A leave-one-SNP-out test was performed to determine whether the MR results were affected by a single nucleotide polymorphism (SNP). The weighted median method was conducted to further validate our results. Results: Based on IVW, MR-Egger and weighted median models, we found no causal association between iron status (ferritin, iron, total iron binding capacity, or transferrin saturation) and OP (P Conclusion: Our results demonstrate that there is no genetic causal association between OP and iron status, but the effects of other factors were not excluded.