ИСТИНА

Background/Objectives: Stroke is the second cause of death worldwide. Despite a few dozens of genomic loci found to be associated with the ischemic stroke (IS), the genetic bases of the disease remain underexplored. We applied clustering methods to genome-wide data of 5580 individuals with IS and controls to search for genetic loci (groups of single nucleotide polymorphisms, SNPs) associated with the risk of IS. Methods: The genotypes of 883908 SNPs were transformed into autosome based linkage disequilibrium matrices and clustered with DBSCAN and HDBSCAN algorithms. Haplotypes were inferred for each cluster and tested for association with IS using Plink, p-values were adjusted by the total number of clusters revealed. The sets of SNPs associated significantly with IS were annotated. Genes obtained were tested for overrepresentation in sets of human genes given in MSigDB. Results: There were identified 97 and 122 candidate genes by DBSCAN and HDBSCAN, respectively, and 88 of which were common. Sixteen genes of protocadherin gamma gene cluster were found to be overrepresented in cell adhesion. Conclusion: To date little is known about the role of protocadherin genes in IS but there are several studies showing their involvement into neurodevelopmental disorders. Our research showed for the first time the association of several protocadherin genes of gamma subfamily with IS. This suggests protocadherins can be a common part of base mechanisms underlying pathological processes in nervous system. Grant: The study was funded by Russian Foundation for Basic Research (grant No 19-29- 01151)