The role of NSAID in mediating the effect of genetically predicted major depressive disorder on osteomyelitis: A Mendelian randomization study

Background: Osteomyelitis and major depressive disorder (MDD) are significant health concerns with potential interconnections. However, the underlying mechanisms linking these conditions remain unknown. This study aimed to investigate the potential mediating role of non-steroidal anti-inflammatory drug (NSAID) medication in the association between MDD and the risk of osteomyelitis. Methods: We utilized summary data from large-scale genome-wide association studies (GWAS) to perform Mendelian randomization (MR) mediation analysis. Instrumental variables were selected based on genome-wide significance, and instrumental strength was assessed using F-statistics. Univariable and multivariable MR analyses were conducted to estimate causal effects and proportions mediated by NSAID medication. Results: The univariable MR analysis revealed significant associations between MDD and osteomyelitis (odds ratio [OR] = 1.44, 95 % confidence interval [CI]: 1.18-1.874) and between MDD and NSAID medication (OR = 1.36, 95 % CI 1.24-1.49). In the multivariable MR analysis, the direct effect of MDD on osteomyelitis was OR 1.35 (95 % CI: 1.09, 1.67) after adjusting for NSAID medication. The proportion of mediation by NSAID medication was 23 % (95 % CI: 0.05 %, 38.6 %). Conclusion: This MR study provides evidence for a genetically predicted causal association between MDD, NSAID medication, and osteomyelitis. The findings emphasize the need for a comprehensive approach in managing individuals with comorbid depression and osteomyelitis, considering the potential risks and benefits of NSAID medication. Future research should address limitations and explore additional mediators and confounding factors to enhance understanding of this complex relationship.