Cognitive function and knee osteoarthritis: A bidirectional Mendelian randomization study with BMI mediation

Area of Science:

• Genetics
• Epidemiology
• Orthopedics

Background:

• Knee osteoarthritis (KOA) is a prevalent degenerative joint disease with complex etiology.
• The potential causal link between cognitive function and KOA remains incompletely understood.
• Investigating mediating factors like body mass index (BMI) is crucial for understanding this relationship.

Purpose of the Study:

• To investigate the bidirectional causal relationship between cognitive function and KOA using Mendelian randomization (MR).
• To examine whether BMI mediates the causal effect of cognitive function on KOA.
• To identify potential targets for KOA prevention strategies.

Main Methods:

• Bidirectional Mendelian randomization (MR) analysis utilizing genome-wide association study summary statistics.
• Primary analysis employed the inverse-variance weighted (IVW) method.
• Sensitivity analyses included MR-Egger, weighted median, robust adjusted profile score, and MR-PRESSO.

Main Results:

• Forward MR indicated a significant inverse causal effect of cognitive function on KOA risk (intelligence and cognitive performance associated with reduced KOA risk).
• Reverse MR analyses revealed no evidence of a causal effect of KOA on cognitive function.
• Mediation analysis demonstrated that BMI partially mediates the effect of intelligence on KOA, explaining 27.29% of the total effect.

Conclusions:

• Cognitive function exerts a unidirectional causal influence on KOA risk.
• Body mass index (BMI) acts as a partial mediator in the relationship between cognitive function and KOA.
• Findings underscore the importance of cognitive health and weight management in mitigating KOA risk.