Integrating Genome-Wide Association Study and Brain Expression Data Highlights Cell Adhesion Molecules and Purine Metabolism in Alzheimer's Disease
Integrating Genome-Wide Association Study and Brain Expression Data Highlights Cell Adhesion Molecules and Purine Metabolism in Alzheimer's Disease
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DOI：
10.1007/s12035-014-8884-5
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发表时间：
2015-08-01
影响因子：
5.1
通讯作者：
Liu, Guiyou
中科院分区：
文献类型：
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作者：
Xiang, Zimin;Xu, Meiling;Liu, Guiyou
阿尔茨海默病是老年人最常见的神经退行性疾病。近年来，全基因组关联研究（GWAS）被用于研究AD的发病机制。然而，很大一部分阿尔茨海默病的遗传性尚未得到解释。我们之前发现细胞粘附分子（CAM）途径在两个AD GWAS中是一致的信号。然而，目前尚不清楚CAM是否存在于阿尔茨海默病遗传和环境风险联盟（GERAD） GWAS和脑表达GWAS中。同时，我们认为整合AD GWAS和AD脑表达数据集可能为识别AD的重要通路提供补充信息。在这里，我们进行了系统分析，使用(1)KEGG通路，(2)来自GERAD的大规模AD GWAS (n = 11,789),(3)来自AD小脑和颞叶皮层的两个大脑表达GWAS数据集（n = 399），以及(4)AD GWAS通路分析的先前结果。结果表明：(1)CAM在5个AD GWAS中是一致的信号；(2) CAM是AD中最显著的信号；(3)我们确认了先前与免疫系统和疾病、心血管疾病等相关的AD风险通路；(4)首次强调了阿尔茨海默病的嘌呤代谢途径。我们相信我们的结果可能会促进我们对阿尔茨海默病机制的理解，并将为未来阿尔茨海默病的遗传研究提供非常有用的信息。
Alzheimer's disease (AD) is the most common neurodegenerative disease in the elderly. Recently, genome-wide association studies (GWAS) have been used to investigate AD pathogenesis. However, a large proportion of AD heritability has yet to be explained. We previously identified the cell adhesion molecule (CAM) pathway as a consistent signal in two AD GWAS. However, it is unclear whether CAM is present in the Genetic and Environmental Risk for Alzheimer's Disease Consortium (GERAD) GWAS and brain expression GWAS. Meanwhile, we think integrating AD GWAS and AD brain expression datasets may provide complementary information to identify important pathways involved in AD. Here, we conducted a systems analysis using (1) KEGG pathways, (2) large-scale AD GWAS from GERAD (n = 11,789), (3) two brain expression GWAS datasets (n = 399) from the AD cerebellum and temporal cortex, and (4) previous results from pathway analysis of AD GWAS. Our results indicate that (1) CAM is a consistent signal in five AD GWAS; (2) CAM is the most significant signal in AD; (3) we confirmed previous AD risk pathways related to immune system and diseases, and cardiovascular disease, etc.; and (4) we highlighted the purine metabolism pathway in AD for the first time. We believe that our results may advance our understanding of AD mechanisms and will be very informative for future genetic studies in AD.