Genetically predicted type 2 diabetes may be a protective factor for bone mineral density：A Mendelian randomization study

Abstract

Purpose: The aim of this study was to investigate the causal association between T2D and BMD using MR analysis. Methods: We obtained genetic data for T2D and BMD from previously published genome-wide association studies (GWAS). We selected single nucleotide polymorphisms (SNPs) with significant genome-wide differences(p<5×10-8) and independent (r2 < 0.001), and further analysed SNPs with F ≥ 10. To assess causality, we used inverse variance weighting (IVW) and reported results as odds ratios (ORs). We also tested for heterogeneity using Cochran's Q, tested for polymorphism using the MR-Egger intercept, and performed sensitivity analyses to ensure the robustness of our results. Results: The results showed that T2D was significantly associated with FN-BMD(β=0.049, 95%CI 0.021~0.077, p=0.001),LS-BMD(β=0.05, 95%CI 0.015~0.085,p=4.707*10-3), eBMD (β=0.028, 95%CI 0.01~0.045,p=0.002), TB-BMD(β=0.040,95%CI 0.015~0.064,p =0.002),TB-BMD(age over 60)(β=0.051,95%CI 0.016~0.086,p = 0.004),TB-BMD (age 45-60) (β=0.05,95%CI 0.014~0.087,p=0.007). Conclusion: In summary, our study suggests that T2D may act as a protective factor for BMD, we do not have sufficient evidence to support a causal effect of T2D on BMD at a genetically predicted level. More cases need to be included for analysis.