Does enhanced cognitive performance reduce fracture risk? a Mendelian randomization study

Objective: While observational studies have suggested a link between cognitive performance and fracture risk, the causality and site-specific nature are unclear. We applied Mendelian randomization (MR) to elucidate these associations.Methods: 147 single-nucleotide polymorphisms (SNPs) tied strongly to cognitive performance (p< 5e-8) were selected. We performed MR analysis to investigate the causal relationship between cognitive performance and fractures at specific sites, including the wrist, upper arm, shoulder, ribs, sternum, thoracic spine, lumbar spine, pelvis, femur, leg, and ankle. The primary estimate was determined using the inverse variance-weighted method. Additionally, we examined heterogeneity using the MR Pleiotropy RESidual Sum Outlier test and Cochran Q, and employed MR-Egger regression to identify horizontal pleiotropy.Results: MR analysis identified a causal association between cognitive performance and fractures at the lumbar-spine-pelvis (odds ratio [OR] = 0.727, 95% CI = 0.552-0.956, p = 0.023), and ribs-sternum-thoracic spine sites (OR = 0.774, 95% CI = 0.615-0.974, p = 0.029). However, no causal association was found for fractures at other sites.Conclusions: This study provided evidence of a causal connection between cognitive performance and fracture risk at certain locations. These findings underline the potential of cognitive enhancement strategies as innovative and effective methods for fracture prevention.