Genetic risk of Spontaneous intracerebral hemorrhage: Systematic review and future directions.

ABSTRACT

BACKGROUND: Although highly heritable, few genes have been linked to spontaneous intracerebral hemorrhage (SICH), which does not currently have any evidence-based disease-modifying therapy. Individuals of African ancestry are especially susceptible to SICH, even more so for indigenous Africans. We systematically reviewed the genetic variants associated with SICH and examined opportunities for rapidly advancing SICH genomic research for precision medicine. METHOD: We searched the National Human Genome Research Institute-European Bioinformatics Institute (NHGRI-EBI) Genome Wide Association Study (GWAS) catalog and PubMed for original research articles on genetic variants associated with SICH as of 15 June 2019 using the PRISMA guideline. RESULTS: Eight hundred and sixty-four articles were identified using pre-specified search criteria, of which 64 met the study inclusion criteria. Among eligible articles, only 9 utilized GWAS approach while the rest were candidate gene studies. Thirty-eight genetic loci were found to be variously associated with the risk of SICH, hematoma volume, functional outcome and mortality, out of which 8 were from GWAS including APOE, CR1, KCNK17, 1q22, CETP, STYK1, COL4A2 and 17p12. None of the studies included indigenous Africans. CONCLUSION: Given this limited information on the genetic contributors to SICH, more genomic studies are needed to provide additional insights into the pathophysiology of SICH, and develop targeted preventive and therapeutic strategies. This call for additional investigation of the pathogenesis of SICH is likely to yield more discoveries in the unexplored indigenous African populations which also have a greater predilection.