Intracranial Aneurysm Working Group

Chair / Co-Chairs: Ynte Ruigrok and Philippe Bijlenga

Aneurysmal subarachnoid hemorrhage (aSAH) is a type of stroke caused by rupture of an intracranial aneurysm.  A twin-based study estimates the heritability of aSAH ~40%. It is considered as a complex disorder with genetic risk factors interacting with environmental factors. Elucidation of the genetic architecture of intracranial aneurysms lags behind such research in most other common diseases, mainly because the genome-wide association studies (GWAS) on the disease are hampered by relatively small samples sizes, as aSAH is rare. To increase the sample size aimed at unravelling more of the disease heritability, we initiated the Intracranial aneurysm working group within the ISGC.  Within this consortium currently GWAS data of up to 13,000 well-phenotyped aneurysm cases are available making it the largest cohort worldwide, and the number is still expanding. This cohort enables us to identify substantially more genetic risk factors for aneurysms and thus make a major contribution to unravelling the genetic architecture of the disease. We are currently finalizing a meta-analysis of the GWAS data. In addition, we aim to perform phenotype-genotype association analyses, including (among other) comparing genotypes between patients with ruptured and unruptured aneurysms. Last, we aim to develop – subgroup specific- polygenic risk scores that can predict aneurysm presence.