1103. Genetic susceptibility to cerebrovascular disease: A systematic review

Authors: Sean Farrell; Cristoph Griessenauer; Atom Sarkar; Ramin Zand; Vida Abedi; Neil Holland; Andrew Michael; Christopher Cummings; Raghu Metpally; Clemens Schirmer; David Carey; Oded Goren (Scranton, PA)


Investigation of genetic susceptibility to cerebrovascular disease has been of growing interest.  The development of large-scale genetic banks allow for in-depth neurogenomic analysis.


A systematic review of human studies assessing neurogenomic aspects of cerebrovascular disease was performed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. Any association study exploring genetic variants located in the exome associated with one of the major cerebrovascular diseases with at least 500 subjects was eligible for inclusion.


Of 6874 manuscripts identified, 35 studies met the inclusion criteria. Most studies of interest focused on ischemic stroke and cerebrovascular occlusive disease. Large cohort genetic association studies on hemorrhagic cerebrovascular disease were less common. In addition to rare, well-established monogenic conditions with significant risk for cerebrovascular disease, a number of genetic variants are also relevant to cerebrovascular pathogenesis as part of a multifactorial process. The 45 polymorphisms identified were located in genes involved in processes related to endothelial and vascular health (15 (33.4%) variants), plasma lipid metabolism (10 (22.2%) variants), inflammation (9 (20%) variants), coagulation (3 (6.7%) variants), and blood pressure modulation (2 (4.4%) variants), and other (6 (13.3%) variants).


This work represents a comprehensive overview of genetic variants in the exome relevant to ischemic and hemorrhagic stroke pathophysiology. Further studies can build off this review to form polygenic risk scores in order to set clinically relevant parameters for stroke prophylaxis and treatment and also broaden our understanding of cerebrovascular neurogenomics.