The association between omega-3 and omega-6 polyunsaturated fatty acids and 3 cardiac inflammatory diseases: A Mendelian randomization study

The Mediterranean diet exerts beneficial effects on cardiovascular health, though many of its underlying mechanisms remain undefined. While omega-3/6 polyunsaturated fatty acids (PUFAs) present in this dietary pattern may influence cardiac inflammatory conditions, their specific roles in heart diseases require further investigation. Independent single nucleotide polymorphisms associated with omega-3/6 PUFAs and 3 cardiac inflammatory diseases were identified through the IEU Open Genome-Wide Association Study database. Mendelian randomization (MR) analysis was employed to assess potential causal relationships between PUFAs and endocarditis, myocarditis, and pericarditis. The primary analytical approach utilized inverse variance weighting (IVW), complemented by weighted median and MR-Egger methods. Sensitivity analyses included Cochran Q test, MR-pleiotropy residual sum and outlier, MR-Egger regression, and leave-one-out analysis to evaluate heterogeneity and potential pleiotropic effects. IVW analysis revealed a positive causal association between omega-6 PUFAs and myocarditis risk ( P -IVW = .013). No statistically significant genetic associations were observed between omega-6 PUFAs and endocarditis or pericarditis. Similarly, omega-3 PUFAs showed no significant causal relationships with any of the 3 inflammatory cardiac conditions. Sensitivity analyses confirmed the absence of horizontal pleiotropy across all findings. This MR study identifies omega-6 fatty acids as a significant class of PUFAs potentially contributing to myocarditis pathogenesis. These findings highlight the need for further investigation into the pro-inflammatory properties of specific PUFAs in cardiac pathophysiology.