Identification Of The Genetic Association Between Ischemic Stroke And Parkinson’s Disease Using Genome-wide Association Study

Objective: Both ischemic stroke(IS)and Parkinson’s disease(PD)are common neurological disorders in aged populations,and there is substantial overlap in their clinical spectrums.The complications of these two diseases weakened self-care ability of the patients,decreased their quality of life,which became the heavy burden of the whole world-wide healthcare.The pathogeneses of the two diseases are complicated,while there is potential association between two diseases in their clinical manifestations and mechanisms.To explain the potential association between IS and PD,our study attempted to investigate the shared susceptible sites by GWAS methods based on genetic view.We hope our research could provide reference value to deepen the comprehension of occurrence and development of two diseases,and help to seek new idea for future early identification and prevention of IS and PD.Methods: 1.By searching and selecting all GWAS studies in neurological field,we collected susceptible SNPs information related to IS or PD.2.We processed the SNPs data by PLINK software and VEGAS online platform to obtain the ischemic stroke related gene set and Parkinson’s disease related gene set and selected the shared gene set.3.Via Web Gestalt online platform,KEGG pathway enriched in IS related gene set and PD related gene set were identified separately and then the shared biological processed involved in both two diseases were uncovered by meta-analysis.Results: 1.There were 9541572 IS related SNPs and 2525704 PD related SNPs obtained from the meta-analysis of several independent GWASs.2.The 9,541,572 selected IS SNPs were assigned to 578 genes by PLINK and 1286 genes by VEGAS2 and the 2,525,704 selected PD SNPs were assigned to 627 genes by PLINK and 1023 genes VEGAS2.There were 33 and 68 shared genes between IS and PD identified from PLINK and VEGAS2.3.After analysis via Web Gestalt,we identified 233 significant IS related KEGG pathways and 37 significant PD related KEGG pathways.There were 4 IS and PD shared pathways uncovered after meta-analysis associated with cellular community,immune system and signal transduction.Conclusions: Ischemic stroke is an acute ischemic cerebrovascular disease associated with age,gender,ethnicity,genetics,hypertension,diabetes mellitus,dyslipidemia and smoking,etc.Parkinson’s disease is the second common neurodegenerative disease related to the interaction of environment factors,genetics and aging of nervous system.Many patients suffered from IS and PD at the same time,which indicated the potential association between two diseases.Based on the bioinformatics method,our research studied the large amount of SNPs systematically.At the meanwhile,to investigate the shared molecular mechanism,we compared the gene based test and pathway analysis of these two diseases and explored the common genes and pathways deeply.O ur results indicated that the identified common biological pathway of IS and PD were associated with signaling pathways regulating pluripotency of stem cells,leukocyte transendothelial migration,TGF-beta signaling pathway and tight junction,suggesting that the pathogenesis and overlap of IS and PD could be related to cell signal transduction and immune system.Our study compared and provided the evidence of the potential shared genetic mechanism of IS and PD for the first time,and offered the reference for the future study in neurologic disorder field.