Abstract：
Alzheimer\'s Disease (AD) is the most common form of dementia, affecting cognitive and behavioral functions. AD is a complex disease resulting from the modest effect of gene interaction and environmental factors, as a result of which the exact pathogenesis is still unknown.
The aim of the present study was to investigate the association between variants of 98 targeted genes with Alzheimer\'s disease phenotype.
A total of 98 genes from 32 AD cases and 11 controls were genotyped using the Haloplex target enrichment method and the PCR-RFLP approach.Association analysis was performed using the PLINK tool to identify the variant significantly associated with AD. Functional enrichment analysis and network analysis was performed using ClueGo and String database respectively. The Expression Quantitative Trait Loci (eQTL) analysis using the Genotype Tissue Expression (GTEx) dataset to explore the possible implication of the variant on the expression of one or more genes in different brain regions and whole blood.
Association analysis showed significant association of 19 variant assigned to 16 genes with Alzheimer\'s with p-value < 0.05 with rs367398/NOTCH4 only variant that passed multiple test corrections. Functional enrichment analysis showed association of these genes with AD. ClueGo and network analysis utilizing the String database suggested that genes are directly and indirectly linked to the AD pathogenesis. eQTL analysis revealed that the rs367398/NOTCH4 and rs1799806/ACHE variant showed significant eQTL for the neighbouring genes.
The present study showed the possible role of 16 genes in AD pathogenesis, especially highlighting the role of rs367398/NOTCH4 and rs1799806/ACHE. However further investigation with large cohort is required to study and validate the implication of these variants in the AD pathogenesis.
The aim of the present study was to investigate the association between variants of 98 targeted genes with Alzheimer\'s disease phenotype.
A total of 98 genes from 32 AD cases and 11 controls were genotyped using the Haloplex target enrichment method and the PCR-RFLP approach.Association analysis was performed using the PLINK tool to identify the variant significantly associated with AD. Functional enrichment analysis and network analysis was performed using ClueGo and String database respectively. The Expression Quantitative Trait Loci (eQTL) analysis using the Genotype Tissue Expression (GTEx) dataset to explore the possible implication of the variant on the expression of one or more genes in different brain regions and whole blood.
Association analysis showed significant association of 19 variant assigned to 16 genes with Alzheimer\'s with p-value < 0.05 with rs367398/NOTCH4 only variant that passed multiple test corrections. Functional enrichment analysis showed association of these genes with AD. ClueGo and network analysis utilizing the String database suggested that genes are directly and indirectly linked to the AD pathogenesis. eQTL analysis revealed that the rs367398/NOTCH4 and rs1799806/ACHE variant showed significant eQTL for the neighbouring genes.
The present study showed the possible role of 16 genes in AD pathogenesis, especially highlighting the role of rs367398/NOTCH4 and rs1799806/ACHE. However further investigation with large cohort is required to study and validate the implication of these variants in the AD pathogenesis.
摘要：
背景：阿尔茨海默病（AD）是最常见的痴呆症，影响认知和行为功能。AD是一种复杂的疾病，由基因相互作用和环境因素的适度作用引起，因此，确切的发病机制仍然未知。
目的：本研究的目的是研究98个靶基因的变异与阿尔茨海默病表型之间的关联。
方法：使用Haloplex靶富集方法和PCR-RFLP方法对来自32例AD病例和11例对照的98个基因进行了基因分型。使用PLINK工具进行关联分析以鉴定与AD显著相关的变体。分别使用ClueGo和String数据库进行功能富集分析和网络分析。使用基因型组织表达(GTEx)数据集进行表达定量性状基因座(eQTL)分析,以探索变体对不同脑区和全血中一个或多个基因表达的可能影响。
结果：关联分析显示，分配给16个基因的19个变异与阿尔茨海默病显著相关，p值<0.05，rs367398/NOTCH4仅变异通过多次测试校正。功能富集分析表明与AD相关的基因。ClueGo和利用String数据库的网络分析表明，基因与AD发病机理直接和间接相关。eQTL分析表明，rs367398/NOTCH4和rs1799806/ACHE变体对相邻基因显示出明显的eQTL。
结论：本研究显示16个基因在AD发病机制中的可能作用。尤其突出了RS367398/NOTCH4和RS1799806/ACHE的作用。然而，需要对大型队列进行进一步研究，以研究和验证这些变体在AD发病机理中的意义。
目的：本研究的目的是研究98个靶基因的变异与阿尔茨海默病表型之间的关联。
方法：使用Haloplex靶富集方法和PCR-RFLP方法对来自32例AD病例和11例对照的98个基因进行了基因分型。使用PLINK工具进行关联分析以鉴定与AD显著相关的变体。分别使用ClueGo和String数据库进行功能富集分析和网络分析。使用基因型组织表达(GTEx)数据集进行表达定量性状基因座(eQTL)分析,以探索变体对不同脑区和全血中一个或多个基因表达的可能影响。
结果：关联分析显示，分配给16个基因的19个变异与阿尔茨海默病显著相关，p值<0.05，rs367398/NOTCH4仅变异通过多次测试校正。功能富集分析表明与AD相关的基因。ClueGo和利用String数据库的网络分析表明，基因与AD发病机理直接和间接相关。eQTL分析表明，rs367398/NOTCH4和rs1799806/ACHE变体对相邻基因显示出明显的eQTL。
结论：本研究显示16个基因在AD发病机制中的可能作用。尤其突出了RS367398/NOTCH4和RS1799806/ACHE的作用。然而，需要对大型队列进行进一步研究，以研究和验证这些变体在AD发病机理中的意义。
