Title:Headache and Intracranial Aneurysm: A Bidirectional Mendelian Randomization Study
Volume: 22
Issue: 1
Author(s): Chunlin Ren, Qian Gao, Xinmin Li, Fangjie Yang, Jing Wang, Pengxue Guo, Zhenfei Duan, YuTing Kong, MengYao Bi, Lidian Chen and Yasu Zhang*
Affiliation:
- Rehabilitation Medicine College, Henan University of Chinese Medicine, Zhengzhou, Henan, China
Keywords:
Headache, migraine, intracranial aneurysm, mendelian randomization, single nucleotide polymorphism, causal link.
Abstract:
Introduction: Headaches affect up to 95% of individuals during their lifetime and are
a major global cause of disability. Intracranial Aneurysm (IA) is a cerebrovascular disorder affecting
approximately 3.2% of the general population. Observational studies have suggested an
association between headaches and IA, but the causal relationship remains unclear. This Mendelian
Randomization (MR) analysis aims to elucidate the causal relationship between headaches
and IA.
Methods: A two-sample bidirectional Mendelian Randomization (MR) analysis was performed
using publicly available Genome-Wide Association Study (GWAS) data to assess the causal relationships
between IA and four headache subtypes, namely, Chronic Headache (CH), Tension-
Type Headache (TTH), Migraine Without Aura (MO), and Migraine With Aura (MA). The inverse
variance weighted method was employed as the primary method, with sensitivity analyses
conducted to evaluate the robustness of the results. Mediation analysis was performed to investigate
the potential mediating role of hypertension.
Results: The MR analysis revealed that MO was associated with an increased risk of aneurysmal
Subarachnoid Hemorrhage (aSAH) (Odds Ratio [OR] = 1.422, 95% Confidence Interval [CI]:
1.0541.918, and P = 0.021), while MA (OR = 1.527, 95% CI: 1.1152.091, and P = 0.008) was
associated with an elevated risk of unruptured IA (uIA). Mediation analysis indicated that hypertension
did not significantly mediate these associations.
Discussion: This study highlights the potential role of MO in aSAH and MA in uIA, where hypertension
does not serve as a significant mediator. Further research is necessary to investigate
the underlying mechanisms, which may offer valuable insights into the prevention and management
of IA.
Conclusion: Bidirectional MR analysis of four headache subtypes and IA provides evidence that
MO is associated with an increased risk of aSAH, while MA is linked to a higher risk of uIA.
These findings contribute to a better understanding of the complex relationship between headaches
and IA.
