Causal relationship between 179 plasma lipids and intracranial aneurysm: A 2-sample Mendelian randomization study

Current evidence suggests that the deposition of lipid plaques is frequently observed in the walls of intracranial aneurysms (IAs). Therefore, the objective of this research was to determine the causal link between plasma lipids and IAs. Genetic instrumental variables for 179 plasma lipids were acquired from a genome-wide association study of 7174 unrelated Finnish individuals. Outcome data for individuals with IAs were retrieved from a genome-wide association study involving 23 cohorts, comprising 79,429 individuals of European ancestry. An inverse-variance weighted method was employed as the key analysis method. To ensure the reliability of the findings, Mendelian randomization (MR)-Egger regression, weighted-median, and weighted-mode methods were employed. Sensitivity analyses included Cochran Q test, MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO), Radial MR test, MR-Egger intercept test, and leave-one-out analysis. Following rigorous screening, MR tests, and Bonferroni correction, the genetically predicted level of phosphatidylethanolamine (18:2_0:0) (LPE[18:2]) (OR:1.28, P = 1.42 × 10-4), phosphatidylcholine (PC) (16:0_20:4) (OR:0.86, P = 1.38 × 10-4), PC (18:0_20:3) (OR:1.29, P = 2.33 × 10-4), and PC (O-16:0_20:4) (OR:0.83, P = 2.22 × 10-4) showed significant causal relationships with aSAH. Two plasma lipids, LPE (18:2) (OR:1.22, P = 3.14 × 10-5) and PC (16:1_18:2) (OR:1.19, P = 1.53 × 10-4) exhibited a positive correlation with the risk of IAs. No significant causal link was found between 179 plasma lipids and uIA. Genetically determined LPE (18:2), PC (18:0_20:3), and PC (16:1_18:2) can increase the risk of IAs rupture; while PC (16:0_20:4) and PC (O-16:0_20:4) can reduce the risk of IAs rupture. PCs with arachidonic acid chains and the metabolism of arachidonic acid may be crucially involved in the occurrence and development of IAs.