Genetically predicted cognitive performance and risk of meniscal derangement: A 2-sample Mendelian randomization study

The causal relationship between cognitive performance and meniscal derangement is unclear. This study aims to investigate the potential genetic association between cognitive performance and meniscal derangement. We conducted a 2-sample Mendelian randomization (MR) analysis utilizing summary-level data from extensive genome-wide association studies. Single nucleotide polymorphisms (SNPs) achieving genome-wide significance ( P  < 5 × 10 ⁻⁸ ) were employed as instrumental variables for each exposure. The inverse-variance weighted (IVW) method served as the principal statistical technique, complemented by the weighted median, MR-Egger regression, and MR-PRESSO methods for sensitivity analyses, accommodating some of the assumptions inherent in IVs. Genetically predicted cognitive performance was inversely correlated with the odds of meniscal derangement. However, the MR-Egger regression analysis did not show a statistically significant association. The IVW method yielded an odds ratio (OR) of 0.76 (95% CI: 0.66–0.88, P  = .0002) per standard deviation increase in genetically predicted cognitive performance. The weighted median method showed a directionally consistent association (OR = 0.81, 95% CI: 0.67–0.98, P  = .030). Additionally, no evidence of directional horizontal pleiotropy was detected using the MR-Egger intercept ( P  > .05). Significant heterogeneity was observed across SNP-specific estimates ( P  < .05). This 2-sample MR study suggests that higher genetically predicted cognitive performance is associated with a lower risk of meniscal derangement. Further studies are warranted to validate this association and clarify the underlying neurocognitive and musculoskeletal mechanisms.