Implication of the Immune System in Alzheimer's Disease: Evidence from Genome-Wide Pathway Analysis
Implication of the Immune System in Alzheimer's Disease: Evidence from Genome-Wide Pathway Analysis
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DOI：
10.3233/jad-2010-100018
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发表时间：
2010-01-01
影响因子：
4
通讯作者：
Amouyel, Philippe
中科院分区：
文献类型：
--
作者：
Lambert, Jean-Charles;Grenier-Boley, Benjamin;Amouyel, Philippe
最近发表了阿尔茨海默病（AD）领域的几项全基因组关联研究（GWAS）的结果。尽管这些研究详细报道了单核苷酸多态性（SNP）和与AD相关的最强证据的邻近基因，但很少关注基因组的其他部分。然而，互补的统计学和生物信息学方法现在能够从仅名义上与疾病风险相关的其他SNP和/或基因中提取相关信息。使用两种不同的工具（ALIGATOR和GenGen/KEGG软件包）分析了包含2，032例AD病例和5，328例对照的大型GWAS数据集。两种基因集富集方法的收敛输出表明AD中存在免疫系统功能障碍。此外，尽管这些统计方法没有采用关于生物学功能在疾病过程中的假定作用的先验假设，但与AD风险相关的基因在“阿尔茨海默病”KEGG途径中被过度表达。总之，使用GWAS数据集对生物学途径进行系统搜索似乎可以安慰已经怀疑的主要原因，但可能特别强调免疫系统在AD中的重要性。
The results of several genome-wide association studies (GWASs) in the field of Alzheimer's disease (AD) have recently been published. Although these studies reported in detail on single-nucleotide polymorphisms (SNPs) and the neighboring genes with the strongest evidence of association with AD, little attention was paid to the rest of the genome. However, complementary statistical and bio-informatics approaches now enable the extraction of pertinent information from other SNPs and/or genes which are only nominally associated with the disease risk. Two different tools (the ALIGATOR and GenGen/KEGG software packages) were used to analyze a large GWAS dataset containing 2,032 AD cases and 5,328 controls. Convergent outputs from the two gene set enrichment approaches suggested an immune system dysfunction in AD. Furthermore, although these statistical approaches did not adopt a priori hypotheses concerning a biological function's putative role in the disease process, genes associated with AD risk were overrepresented in the "Alzheimer's disease" KEGG pathway. In conclusion, a systematic search for biological pathways using GWAS data set seems to comfort the primary causes already suspected but may specifically highlight the importance of the immune system in AD.