Mendelian randomization analysis does not reveal a causal influence of mental diseases on osteoporosis

Abstract

Introduction: Osteoporosis (OP) is primarily diagnosed through bone mineral density (BMD) measurements, and it often leads to fracture. Observational studies suggest that several mental diseases (MDs) may be linked to OP, but the causal direction of these associations remain unclear. This study aims to explore the potential causal association between five MDs (Schizophrenia, Depression, Alzheimer's disease, Parkinson's disease, and Epilepsy) and the risk of OP.

Methods: First, single-nucleotide polymorphisms (SNPs) were filtered from summary-level genome-wide association studies using quality control measures. Subsequently, we employed two-sample Mendelian randomization (MR) analysis to indirectly analyze the causal effect of MDs on the risk of OP through bone mineral density (in total body, femoral neck, lumbar spine, forearm, and heel) and fractures (in leg, arm, heel, spine, and osteoporotic fractures). Lastly, the causal effect of the MDs on the risk of OP was evaluated directly through OP. MR analysis was performed using several methods, including inverse variance weighting (IVW)-random effects, IVW-fixed effects, maximum likelihood, weighted median, MR-Egger regression, and penalized weighted median.

Results: The results did not show any evidence of a causal relationship between MDs and the risk of OP (with almost all P values > 0.05). The robustness of the above results was proved to be good.

Discussion: In conclusion, this study did not find evidence supporting the claim that MDs have a definitive impact on the risk of OP, which contradicts many existing observational reports. Further studies are needed to determine the potential mechanisms of the associations observed in observational studies.

Keywords: Mendelian randomization; genome-wide association study; mental diseases; osteoporosis; osteoporosis fracture.