Causal relationship between chronic obstructive pulmonary disease and BMD at different sites: A bidirectional Mendelian randomization study

Abstract

Observational studies have demonstrated a correlation between chronic obstructive pulmonary disease (COPD) and osteoporosis (OP). However, it is unclear whether there is genetic causality between COPD and bone mineral density (BMD) reduction at different sites. This study assessed the causal relationship between COPD and BMD in various anatomical locations. Data associated with COPD and BMD were obtained from published genome-wide association studies (GWAS). We selected single nucleotide polymorphisms (SNPs) that were strongly associated with COPD and BMD could serve as instrumental variables for the analysis. Inverse variance weighted, MR-Egger and weighted median were manipulated to evaluate causality. Subsequently, we conducted heterogeneity tests using Cochran Q test and tested for pleiotropy using the MR-Egger intercept. We performed leave-one-out sensitivity analysis to assess the robustness of the results. Additionally, we obtained more accurate causal genetic associations by removing any pleiotropic outlying SNPs and performed Mendelian randomization (MR) analysis with the remaining data. Our findings established that COPD was negatively associated with Heel-BMD (odds ratio[OR] = 0.978, 95% confidence interval [CI] = 0.966, 0.990, P = .0003) but not LS-BMD (OR = 0.981, 95% CI: 0.943, 1.020, P = .335), FA-BMD (OR = 0.984, 95% CI: 0.927, 1.046, P = .616), and FN-BMD (OR = 0.981, 95% CI: 0.950, 1.014, P = .249). In reverse MR analysis, the results showed no significant causal effect of BMD at different sites on COPD. The results were proved to be dependable and steady by sensitivity, heterogeneity, and pleiotropy analysis. We found that COPD increases the risk of decreased heel BMD, however, there is no evidence that the loss of BMD increases the risk of COPD.