The causal relationship between Omega-3 fatty acids and Achilles Tendinitis risk: A two-sample Mendelian randomization study in European populations

Omega-3 fatty acids, found in fish oil, flaxseed oil, and walnuts, are widely known for their anti-inflammatory properties and are used in the treatment of various inflammatory diseases. While their benefits in cardiovascular diseases and arthritis are well-documented, their role in musculoskeletal conditions, particularly Achilles tendinitis, remains unclear. This study investigates the causal relationship between Omega-3 fatty acids and the risk of Achilles tendinitis using a two-sample Mendelian randomization approach. Genetic variants associated with Omega-3 levels were selected from publicly available genome-wide association study data. Nineteen independent single nucleotide polymorphisms were used as instrumental variables to predict Omega-3 levels. The causal relationship between genetically predicted Omega-3 levels and Achilles tendinitis risk was evaluated using inverse variance weighting, MR-Egger regression, and weighted median methods. Sensitivity analyses, including leave-one-out analysis and funnel plots, were performed to assess robustness. The main analysis showed that for each 1 standard deviation increase in genetically predicted Omega-3 levels, the risk of Achilles tendinitis increased by 18% (odds ratio = 1.18, P = .020). Consistent results were observed across multiple robust methods, although only the inverse variance weighting method reached nominal significance. Sensitivity analyses confirmed that the results remained stable even when individual single nucleotide polymorphisms were excluded, and there was no significant evidence of horizontal pleiotropy or heterogeneity. This study suggests a potential causal relationship between Omega-3 fatty acids and the risk of Achilles tendinitis. Despite the small effect size and lack of statistical significance after multiple testing corrections, these findings warrant further investigation. Larger sample sizes and analyses of different Omega-3 subtypes are needed to confirm these results and explore their potential clinical implications in tendon diseases.