[Study on the genetic correlation between polyunsaturated fatty acids and knee osteoarthritis]

Objective: To explore the shared genetic basis and potential causal relationships between polyunsaturated fatty acids (PUFAs)-including n-3 PUFAs, docosahexaenoic acid (DHA), n-6 PUFAs, and linoleic acid (LA) and knee osteoarthritis (KOA). Methods: Based on genome-wide association studies for PUFAs (n=136 016) and KOA (n=396 054), we conducted genetic correlation, cross-trait association, and Mendelian randomization (MR) analyses, controlling for potential confounders such as BMI and bone mineral density. Results: Five region-specific signals were identified between PUFAs and KOA at the genomic level. Cross-trait analyses revealed 70 pleiotropic loci, of which five were novel and all related to n-6 PUFAs. MR analyses demonstrated that higher genetically predicted levels of n-6 PUFAs (OR=0.93, 95%CI:0.88-0.98, P=7.11×10⁻³) and LA (OR=0.92, 95%CI:0.87-0.97, P=2.60×10⁻³) were significantly associated with reduced risk of KOA. These protective effects remained robust in multivariable MR. Conclusion: n-6 PUFAs and their subtype LA exert protective effects against the development and progression of KOA.