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Headache and Intracranial Aneurysm: A Bidirectional Mendelian Randomization Study
Chunlin Ren1, Qian Gao2, Xinmin Li3
1Rehabilitation Medicine College, Henan University of Chinese Medicine, Zhengzhou, Henan, China.
Insights
Migraine Without Aura increases the risk of aneurysmal Subarachnoid Hemorrhage, while Migraine With Aura is linked to unruptured Intracranial Aneurysm. Hypertension was not a significant mediator in these headache and aneurysm relationships.
Area of Science:
- Neuroscience
- Genetics
- Epidemiology
Background:
- Headaches are a prevalent cause of disability, affecting up to 95% of people.
- Intracranial Aneurysm (IA) is a serious cerebrovascular condition affecting approximately 3.2% of the population.
- The causal link between headaches and IA requires further investigation.
Purpose of the Study:
- To investigate the causal relationship between headaches and Intracranial Aneurysm (IA).
- To examine four headache subtypes: Chronic Headache (CH), Tension-Type Headache (TTH), Migraine Without Aura (MO), and Migraine With Aura (MA).
- To assess the potential mediating role of hypertension in these associations.
Main Methods:
- A two-sample bidirectional Mendelian Randomization (MR) analysis was conducted.
- Genome-Wide Association Study (GWAS) data was utilized for the analysis.
- Inverse variance weighted method and mediation analysis were employed.
Main Results:
- Migraine Without Aura (MO) showed an association with increased risk of aneurysmal Subarachnoid Hemorrhage (aSAH).
- Migraine With Aura (MA) was linked to an elevated risk of unruptured IA (uIA).
- Hypertension was not found to be a significant mediator.
Conclusions:
- MO may play a role in aSAH, and MA may be associated with uIA.
- These findings enhance the understanding of the complex relationship between headaches and IA.
- Further research is needed to explore underlying mechanisms for prevention and management.
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]: 1.054.1.918, and P = 0.021), while MA (OR = 1.527, 95% CI: 1.115.2.091, 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.
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