Causal Relationship between Type 2 Diabetes Mellitus and Osteoporosis : A Mendelian Randomization Study in an Asian Population

Multiple mendelian randomization studies in European populations have reported a positive relationship between type 2 diabetes mellitus (T2DM) and bone mineral density. However, it remains unknown whether such relationship exists in Asian populations remains unclear because the risk of osteoporosis differs among different ethnic groups. Thus, we used a Mendelian randomization (MR) approach to investigate the relationship between T2DM and osteoporosis in Asian populations. GWAS summary data from BioBank Japan were used to identify genetic variants strongly related to T2DM risk (36,614 cases and 155,150 controls) and osteoporosis (7,708 cases and 204,665 controls). Inverse variance-weighted (IVW) analysis was applied and MR-Egger and the weighted median were also used to obtain robust estimates. A series of sensitivity analyses including Cochran’s Q test, MR-Egger regression, leave-one-out analysis, and funnel plots were used to detect pleiotropy or heterogeneity. After rigorous SNP filtering steps in quality control, 81 single nucleotide polymorphisms remained for further analysis. In the main analysis, IVW estimates indicated that T2DM significantly decreased the risk of osteoporosis (odds ratio = 0.93, 95% CI: 0.88–0.99, P = 0.016). Results of MR-Egger and weighted median methods were consistent with IVW estimates. Additionally, the results demonstrated the absence of horizontal pleiotropy and heterogeneity. In conclusion, T2DM significantly decreases the risk of osteoporosis in terms of genetic polymorphism in Asian populations