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Causal relationship between 179 plasma lipids and intracranial aneurysm: A 2-sample Mendelian randomization study
Lu Ding1, Weibiao Cao2, Zhaojun Mei3
1Department of General Practices, The Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, P.R. China.
Medicine
|September 24, 2025
Summary
This study found that specific plasma lipids, including phosphatidylethanolamine (LPE) and phosphatidylcholine (PC), are causally linked to intracranial aneurysms (IAs). Certain LPE and PC variants increase IA rupture risk, while others decrease it, highlighting their role in IA development.
Area of Science:
- Genetics and Cardiovascular Research
- Lipid Metabolism and Vascular Disease
Background:
- Intracranial aneurysms (IAs) are associated with lipid plaque deposition in vessel walls.
- Understanding the causal relationship between plasma lipids and IA development is crucial for risk stratification and potential therapeutic targets.
Purpose of the Study:
- To investigate the causal links between 179 plasma lipids and the risk of intracranial aneurysms (IAs).
- To differentiate the effects of specific lipid profiles on IA occurrence and rupture.
Main Methods:
- Utilized a two-sample Mendelian randomization (MR) approach.
- Employed genetic instrumental variables from a Finnish GWAS for plasma lipids and IA data from a large European ancestry GWAS.
- Applied inverse-variance weighted methods and multiple sensitivity analyses (MR-Egger, weighted-median, MR-PRESSO) to ensure result validity.
Main Results:
- Identified causal relationships between specific phosphatidylethanolamine (LPE[18:2]) and phosphatidylcholine (PC) variants and the risk of aneurysmal subarachnoid hemorrhage (aSAH).
- Found that genetically determined LPE (18:2) and PC (16:1_18:2) positively correlate with IA risk, potentially increasing rupture risk.
- Observed that PC (16:0_20:4) and PC (O-16:0_20:4) show a negative correlation with IA risk, potentially reducing rupture risk. No significant link was found for unruptured IAs (uIA).
Conclusions:
- Specific plasma lipids, particularly those involving arachidonic acid chains within phosphatidylcholines, play a significant causal role in the pathogenesis of intracranial aneurysms.
- Genetically influenced levels of LPE (18:2), PC (18:0_20:3), and PC (16:1_18:2) may elevate IA rupture risk, whereas PC (16:0_20:4) and PC (O-16:0_20:4) might offer protection.
- These findings underscore the importance of lipid metabolism in IA development and suggest potential avenues for future research and clinical intervention.
