Exploring the causal genetic relationship between 41 inflammatory cytokines and osteoporosis: a bidirectional Mendelian randomization analysis.

Objectives: Previous studies reported that many inflammatory factors have associations with osteoporosis. This study use Mendelian randomization (MR) analysis to explore the causal genetic relationship between 41 inflammatory factors and osteoporosis.

Methods: A bidirectional two-sample MR analysis was performed by employing five Mendelian randomization analysis methods including MR Egger regression, weighted median, inverse-variance weighted and weight mode methods. Summary statistics from the genome-wide association study (GWAS) of 41 inflammatory cytokines and osteoporosis were included in this study. This study examined the MR analysis results for heterogeneity and horizontal pleiotropy.

Results: Using the inverse variance weighted (IVW) method, this analysis indicated that elevated monocyte chemotactic protein-1 (MCP-1) levels were potentially linked to a 22% increased likelihood of osteoporosis (Odds Ratio (OR) = 1.22, 95% CI: 1.04-1.43, p = 0.014). Additionally, through the IVW approach, we observed that higher tumor necrosis factor-related apoptosis inducing ligand (TRAIL) levels were possibly associated with a 15% greater risk of osteoporosis (OR = 1.12, 95% CI: 1.03-1.29, p = 0.012). Other 39 inflammatory cytokines don't have casual genetic association with osteoporosis. When this study use MR to estimate the influence of osteoporosis on inflammatory factors, none of the p-values with IVW method were lower than 0.05.

Conclusion: This is the first bidirectional MR analysis to explore the causal genetic relationship between inflammatory cytokines and osteoporosis. This study found that MCP-1 and TRAIL are probably the upstream factors correlated with osteoporosis, and no inflammatory cytokine was involved in osteoporosis development downstream.