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Sharing of Genetic Association Signals by Age-Related Macular Degeneration and Alzheimer's Disease at Multiple Levels.
Molecular Neurobiology ( IF 4.6 ) Pub Date : 2020-08-03 , DOI: 10.1007/s12035-020-02024-y
Handan Tan 1 , Meng Lv 1 , Xiao Tan 1 , Guannan Su 1 , Rui Chang 1 , Peizeng Yang 1
Affiliation  

Age-related macular degeneration and Alzheimer’s disease are closely related complex diseases that may share overlapping pathogenesis in gene networks. This study was conducted to investigate the genetic factors shared by both diseases. We analyzed genome-wide association studies’ summary statistics from both diseases using a new platform known as functional mapping and annotation (FUMA) and a co-localization analysis. We obtained disease-related gene expression profile data from the Gene Expression Omnibus and analyzed these data using weighted gene co-expression network analysis. FUMA analysis and Bayesian co-localization analysis showed that ten genes on chromosome 7, one pathway (complement and coagulation cascade), and forty-two biological processes were common for both diseases. Among these ten genes, two protein-coding genes, two pseudogenes, and two RNA genes were, for the first time, identified to be associated with both diseases. Weighted gene co-expression network analysis identified 19 age-related macular degeneration hub genes and 19 Alzheimer’s disease hub genes and revealed that these two diseases shared nine pathways and 63 biological processes. Using FUMA, co-localization analysis, and weighted gene co-expression network analysis, 10 genes on chromosome 7, 10 pathways, and 105 biological processes were found to be associated with the two degenerative diseases. This suggests that these10 genes and the hub genes of these modules associated with the shared pathways are potential diagnostic markers for both diseases.



中文翻译:

通过年龄相关的黄斑变性和阿尔茨海默氏病在多个层面上共享遗传协会信号。

年龄相关性黄斑变性和阿尔茨海默氏病是密切相关的复杂疾病,可能在基因网络中共享重叠的发病机理。进行这项研究以调查两种疾病共有的遗传因素。我们使用称为功能映射和注释(FUMA)的新平台以及共定位分析,分析了这两种疾病的全基因组关联研究的汇总统计数据。我们从“基因表达综合”获得了疾病相关的基因表达谱数据,并使用加权基因共表达网络分析法对这些数据进行了分析。FUMA分析和贝叶斯共定位分析表明,这两种疾病在7号染色体上有10个基因,一个途径(补体和凝血级联)和42个生物学过程是共同的。在这十个基因中,两个蛋白质编码基因 首次确定两个假基因和两个RNA基因与这两种疾病有关。加权基因共表达网络分析确定了19个与年龄相关的黄斑变性中心基因和19个阿尔茨海默氏病中心基因,并揭示这两种疾病共有9条途径和63个生物学过程。使用FUMA,共定位分析和加权基因共表达网络分析,发现7号染色体上的10个基因,10个途径和105个生物学过程与这两种退行性疾病有关。这表明这些基因和与共享途径相关的这些模块的中枢基因是这两种疾病的潜在诊断标记。加权基因共表达网络分析确定了19个与年龄相关的黄斑变性中心基因和19个阿尔茨海默氏病中心基因,并揭示这两种疾病共有9条途径和63个生物学过程。使用FUMA,共定位分析和加权基因共表达网络分析,发现7号染色体上的10个基因,10个途径和105个生物学过程与这两种退行性疾病有关。这表明这些基因和与共享途径相关的这些模块的中枢基因是这两种疾病的潜在诊断标记。加权基因共表达网络分析确定了19个与年龄相关的黄斑变性中心基因和19个阿尔茨海默氏病中心基因,并揭示了这两种疾病共有9条途径和63个生物学过程。使用FUMA,共定位分析和加权基因共表达网络分析,发现7号染色体上的10个基因,10个途径和105个生物学过程与这两种退行性疾病有关。这表明这些基因和与共享途径相关的这些模块的中枢基因是这两种疾病的潜在诊断标记。发现染色体7、10条途径和105个生物学过程中的10个基因与这两种退化性疾病有关。这表明这些基因和与共享途径相关的这些模块的中枢基因是这两种疾病的潜在诊断标记。发现染色体7、10条途径和105个生物学过程中的10个基因与这两种退化性疾病有关。这表明这些基因和与共享途径相关的这些模块的中枢基因是这两种疾病的潜在诊断标记。

更新日期:2020-09-24
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