Molecular genetics of human intracranial aneurysms

Intracranial aneurysms (IAs) are the dilatations of blood vessels in the brain and pose potential risk of rupture leading to subarachnoid hemorrhage. Although the genetic basis of IAs is poorly understood, it is well-known that genetic factors play an important part in the pathogenesis of IAs. Therefore, the identifying susceptible genetic variants might lead to the understanding of the mechanism of formation and rupture of IAs and might also lead to the development of a pharmacological therapy. To elucidate the molecular pathogenesis of diseases has become a crucial step in the development of new treatment strategies. Although extensive genetic research and its potential implications for future prevention of this often fatal condition are urgently needed, efforts to elucidate the susceptibility loci of IAs are hindered by the issues bewildering the most common and complex genetic disorders, such as low penetrance, late onset, and uncertain modes of inheritance. These efforts are further complicated by the fact that many IA lesions remain asymptomatic or go undiagnosed. In this review, we present and discuss the current status of genetic studies of IAs and we recommend comprehensive genome-wide association studies to identify genetic loci that underlie this complex disease.