Genetic Association Study Between Alzheimer’s Disease And Parkinson’s Disease

Background and Objective: Alzheimer’s disease(AD)and Parkinson’s disease(PD)are the two neurodegenerative diseases which be found in elderly people usually.Both diseases reduce the patients’ self-care ability and the quality of life,and increase the economic burden on families and society.Despite the shared clinical and pathological features of these diseases,the underlying genetic mechanism remains obscure.To explore the shared susceptible genes and genetic pathways between AD and PD,we used GWAS to perform analysis in-depth.GWAS help us to understand the occurrence and development of these two diseases deeply,and beneficially to identify two diseases early and seek new ideas for future prevention.Participants and methods: Making use of data from two published GWAS datasets on AD(8,309 AD cases,7,366 normal cognitive controls,2,312,887 SNPs)and PD(4,238 PD cases,4,239 controls,2,525,704 SNPs).First,using meta-analysis method implemented in PLINK software and Proxy Gene LD software package,we found out the susceptibility genes of AD and PD respectively which based on gene level of whole genome analysis,and AD-PD shared genes.Second,We used the KEGG pathway in the Web Gestalt database to conduct pathway enrichment analysis on the disease susceptibility gene datasets of AD and PD respectively,and found out the shared genetic pathways.Lastly,in order to further verify the biological significance of these shared pathways between AD and PD in their respective diseases,we investigated the gene expression datasets of AD and PD respectively to find out their differentially expressed genes and explore whether these genes can be enriched in the shared pathways which excavated in the last step.Results:(1)Using PLINK software based on meta-analysis method,we identified 651 AD genes and 627 PD genes.64 shared genes involved in two gene datasets.(2)Using the Proxy Gene LD software,we identified 1016 AD genes and 789 PD genes.56 shared genes involved in two gene datasets.(3)Operated the intersections of AD and PD shared genes obtained by PLINK and Proxy Gene LD methods,we obtained 16 AD and PD shared genes.(4)The gene set obtained by PLINK gene association analysis was analyzed for pathway enrichment,we identified 12 shared pathways between AD and PD.(5)The gene set obtained by Proxy Gene LD gene association analysis was analyzed for pathway enrichment,we identified 28 shared pathways between AD and PD.(6)Operated the intersections of AD and PD shared pathways obtained by PLINK and Proxy Gene LD methods,we obtained ten AD and PD shared pathways finally,which related to immune system diseases[Hematopoietic cell lineage(hsa046400 and Leukocyte transendothelial migration(hsa04670)],environmental information processing [cytokine-cytokine receptor interaction(hsa04060)and Jak-STAT signaling pathway(hsa04630)],cellular processes[Regulation of actin cytoskeleton(hsa04810)and Phagosome(hsa04145)],infectious diseases[Leishmaniasis(hsa05140)and Hepatitis C(hsa05160)],neurodegenerative disease[PD(hsa05012)]and endocrine system[Insulin signaling pathway(hsa04910)].(7)Among ten AD and PD shared pathways,seven pathways showed enrichment of differentially expressed genes in AD gene expression dataset(PD[hsa05012],Regulation of actin cytoskeleton[hsa04810],Phagosome[hsa04145],Hepatitis C[hsa05160],Cytokine-cytokine receptor interaction[hsa04060],Hematopoietic cell lineage [hsa04640] and Jak-STAT signaling pathway [hsa04630],and four pathways showed enrichment of differentially expressed genes in PD gene expression dataset(Regulation of actin cytoskeleton [hsa04810],Leukocyte transendothelial migration [hsa04670],Phagosome[hsa04145] and Jak-STAT signaling pathway [hsa04630]).Conclusion: We have revealed the underlying genetic mechanism of the correlation between AD and PD.Identified ten shared pathways between AD and PD,especially the two immune pathways including Leukocyte transendothelial migration(hsa04670)and Hematopoietic cell lineage(hsa04640),one environmental information processing pathway,the Jak-STAT signaling pathway(hsa04630).Our results provided genetic evidence for further understanding of the genetic mechanisms of AD and PD,and provided a new perspective for the study of their genetic associations deeply.