Lessons learned from whole exome sequencing in multiplex families affected by a complex genetic disorder, intracranial aneurysm.

Genetic risk factors for intracranial aneurysm (IA) are not yet fully understood. Genomewide association studies have been successful at identifying common variants; however, the role of rare variation in IA susceptibility has not been fully explored. In this study, we report the use of whole exome sequencing (WES) in seven densely-affected families (45 individuals) recruited as part of the Familial Intracranial Aneurysm study.

Affected twins in the familial intracranial aneurysm study.

Background And Purpose: Very few cases of intracranial aneurysms (IAs) in twins have been reported. Previous work has suggested that vulnerability to IA formation is heritable. Twin studies provide an opportunity to evaluate the impact of genetics on IA characteristics, including IA location.

Genome-wide association study of intracranial aneurysm identifies a new association on chromosome 7.

Background And Purpose: Common variants have been identified using genome-wide association studies which contribute to intracranial aneurysms (IA) susceptibility. However, it is clear that the variants identified to date do not account for the estimated genetic contribution to disease risk.

Methods: Initial analysis was performed in a discovery sample of 2617 IA cases and 2548 controls of white ancestry.

Apolipoprotein E, statins, and risk of intracerebral hemorrhage.

Background And Purpose: Apolipoprotein E (ApoE) genotypes have been associated with lobar intracerebral hemorrhage (ICH). Although statins have been associated with an increased risk of ICH, meta-analyses have not consistently shown a statin-induced risk of ICH. Here, we test whether hypercholesterolemia (HC) and ApoE polymorphisms affect the risk of ICH by statin use.

Familial intracranial aneurysms: is anatomic vulnerability heritable?

Background And Purpose: Previous studies have suggested that family members with intracranial aneurysms (IAs) often harbor IAs in similar anatomic locations. IA location is important because of its association with rupture. We tested the hypothesis that anatomic susceptibility to IA location exists using a family-based IA study.