The Association Between Genetic Risk Factors and the Size of Intracranial Aneurysms at Time of Rupture

Abstract

BACKGROUND: Genetic risk factors for intracranial aneurysms may influence the size of aneurysms. OBJECTIVE: To assess the association between genetic risk factors and the size of aneurysms at the time of rupture. METHODS: Genotypes of 7 independent single-nucleotide polymorphisms (SNPs) of the 6 genetic risk loci identified in genome-wide association studies of patients with intracranial aneurysms were obtained from 700 Dutch patients with an aneurysmal subarachnoid hemorrhage (1997-2007) previously genotyped in the genome-wide association studies; 255 additional Dutch patients with an aneurysmal subarachnoid hemorrhage (2007-2011) were genotyped for these SNPs. Aneurysms were measured on computerized tomography angiography or digital subtraction angiography. The mean aneurysm size (with standard error) was compared between patients with and without a genetic risk factor by the use of linear regression. The association between SNPs and size was assessed for single SNPs and for the combined effect of SNPs by using a weighted genetic risk score. RESULTS: Single SNPs showed no association with aneurysm size, nor did the genetic risk score. CONCLUSION: The 6 genetic risk loci have no major influence on the size of aneurysms at the time of rupture. Because these risk loci explain no more than 5% of the genetic risk, other genetic factors for intracranial aneurysms may influence aneurysm size and thereby proneness to rupture.