Plasma lipidome and intracranial aneurysms: A univariable and multivariable Mendelian randomization study

Recent studies suggest that plasma lipids, including lipoproteins and fatty acids, may contribute to the pathogenesis of intracranial aneurysms (IAs). However, the relationship between a broader range of plasma lipids and IA risk remains unclear. This study uses the Mendelian randomization (MR) approach to explore the causal relationships between 179 plasma lipids and the risk of IAs.

We used summary statistics from a study of 7174 individuals to examine 179 plasma lipids. Data on IAs and aneurysmal subarachnoid hemorrhage (aSAH) were drawn from a study by Bakker MK et al., which included 2070 cases of unruptured IAs, 5 140 cases of aSAH, and 71,934 controls. MR analyses were conducted using inverse variance-weighted as the primary method, with weighted median, weighted mode, and MR-Egger as additional methods. To prioritize lipid risk factors, we applied multivariable Mendelian randomization-Bayesian model averaging.

We identified 5 plasma lipids associated with IAs and 4 with aSAH. Phosphatidylcholine (14:0_18:2) was significantly associated with both IAs and aSAH, with odds ratios of 1.44 (95 % confidence interval [CI] 1.17-1.77, P_adjusted = 0.036) for IAs and 1.53 (95 % CI 1.20-1.94, P_adjusted = 0.036) for aSAH. In multivariable MR, phosphatidylcholine (14:0_18:2) and phosphatidylcholine (18:0_20:3) emerged as the strongest risk factors for IAs and aSAH, respectively.

Our study identifies specific plasma lipids, particularly phosphatidylcholine (14:0_18:2) and phosphatidylcholine (18:0_20:3), as significant risk factors for IAs and aSAH. These findings suggest that phosphatidylcholines could serve as predictive biomarkers for aneurysm risk. Further research is needed to validate these associations and clarify the underlying mechanisms.