Genetically Determined Low-Density Lipoprotein Cholesterol and Risk of Subarachnoid Hemorrhage

Ann Neurol. 2022 Jan;91(1):145-149. doi: 10.1002/ana.26250. Epub 2021 Nov 1.


We evaluated whether genetically elevated low-density lipoprotein cholesterol (LDL-C) levels are associated with lower risk of intracranial aneurysms and subarachnoid hemorrhage (IA/SAH). We conducted a 2-sample Mendelian randomization (MR) study. Our primary analysis used the inverse-variance weighted method. In secondary analyses, we implemented the MR-PRESSO method, restricted our analysis to LDL-C-specific instruments, and performed multivariate MR. A 1-mmol/l increase in genetically instrumented LDL-C levels was associated with a 17% lower risk of IA/SAH (odds ratio = 0.83, 95% confidence interval = 0.73-0.94, p = 0.004). Results remained consistent in secondary and multivariate analyses (all p < 0.05). Our results provide evidence for an inverse causal relationship between LDL-C levels and risk of IA/SAH. ANN NEUROL 2022;91:145-149.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cholesterol, LDL / blood*
  • Cholesterol, LDL / genetics*
  • Humans
  • Mendelian Randomization Analysis
  • Polymorphism, Single Nucleotide
  • Subarachnoid Hemorrhage / blood*
  • Subarachnoid Hemorrhage / genetics*


  • Cholesterol, LDL