Omega-3 fatty acids and intracranial aneurysms: a Mendelian randomization study

IntroductionRecent studies suggest that omega-3 polyunsaturated fatty acids (PUFAs) supplementation benefits for cardiovascular disease and abdominal aortic aneurysms, but its role in intracranial aneurysms (IAs) remains unclear. This study evaluates the effect of omega-3 PUFAs on IAs. Patients and methodsA two-sample Mendelian Randomization study (MR) was conducted to examine the associations between omega-3 PUFAs and IAs, as well as aneurysmal subarachnoid hemorrhage (aSAH). The largest genome-wide association study dataset was used for primary analysis, with replication using independent sources. Two-step MR was used to evaluate the mediating effects of nine aneurysm risk factors and 91 inflammatory cytokines. ResultsHigher genetically predicted levels of total omega-3, omega-3 percentage, and docosahexaenoic acid (DHA) were associated with reduced risks of IAs (combined OR 0.88, 95% CI 0.83-0.94, P<0.001; 0.86, 0.81-0.92, P<0.001; 0.84, 0.78-0.90, P<0.001, respectively) and aSAH (0.85, 0.79-0.91, P=0.009; 0.84, 0.75-0.93, P<0.001; 0.80, 0.71-0.90, P<0.001, respectively). Genetically predicted eicosapentaenoic acid level showed a tendency to increase risk (1.05, 1.01-1.10, P=0.022 for IAs; 1.11, 0.96-1.28, P=0.160 for aSAH). Mediation analysis revealed diastolic blood pressure (DBP) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mediated DHAs effects on IAs (proportion mediated 8.5%, P=0.019; 25.2%, P=0.049) and aSAH (5.7%, P=0.024; 27.5%, P=0.041). ConclusionsOur study suggests that omega-3 PUFAs, particularly DHA, are associated with a reduced risk of IAs and aSAH. This association may be partially mediated by DBP and TRAIL.