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“Genome-wide association study of intracranial aneurysms and aneurysmal subarachnoid haemorrhage”

Research Leader:

Dr. Y.M. Ruigrok

Institution:

University Medical Center (UMC) Utrecht

Background

Aneurysmal subarachnoid hemorrhage (ASAH) is a type of stroke caused by rupture of an intracranial aneurysm (IA).[1] Unlike other cardiovascular diseases, ASAH is more common in women than men; 65% of ASAH and unruptured IA patients are women.[2] We don't fully understand why this is the case, and currently, prevention and treatment of ASAH is the same for women and men. However, it's important to figure out why women are more affected by this condition to ensure all patient are treated optimally.

We previously performed the largest genome-wide association study of IA in over 10,000 cases and 300,000 controls. We identified 17 risk loci and found that more than half the heritability is harbored by common genetic variants.[3] In this project we will perform a new genome-wide association study with an estimated 30,000 cases and 1,800,000 controls. We will focus on sex-differences by performing a sex-stratified association analysis and an X-chromosome analysis. We will assess causal relations between sex-specific clinical and life-style risk factors and ASAH and UIA using Mendelian randomization studies.

References

[1] van Gijn J, Kerr RS, Rinkel GJ. Subarachnoid haemorrhage. Lancet. 2007;369:306-318

[2] Etminan N, Chang HS, Hackenberg K, de Rooij NK, Vergouwen MDI, Rinkel GJE, et al. Worldwide incidence of aneurysmal subarachnoid hemorrhage according to region, time period, blood pressure, and smoking prevalence in the population: A systematic review and meta-analysis. JAMA Neurol. 2019;76:588-597

[3] Bakker MK, (70 more authors), Ruigrok YM. Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors. Nat Genet. 2020 Dec;52(12):1303-1313.