Hu Yang, Zhao Tianyi, Zang Tianyi, Zhang Ying, Cheng Liang
Department of Computer Science and Technology, School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.
Department of Rehabilitation, Heilongjiang Province Land Reclamation Headquarters General Hospital, Harbin, China.
Front Genet. 2019 Jan 25;9:703. doi: 10.3389/fgene.2018.00703. eCollection 2018.
Alzheimer disease (AD) is the fourth major cause of death in the elderly following cancer, heart disease and cerebrovascular disease. Finding candidate causal genes can help in the design of Gene targeted drugs and effectively reduce the risk of the disease. Complex diseases such as AD are usually caused by multiple genes. The Genome-wide association study (GWAS), has identified the potential genetic variants for most diseases. However, because of linkage disequilibrium (LD), it is difficult to identify the causative mutations that directly cause diseases. In this study, we combined expression quantitative trait locus (eQTL) studies with the GWAS, to comprehensively define the genes that cause Alzheimer disease. The method used was the Summary Mendelian randomization (SMR), which is a novel method to integrate summarized data. Two GWAS studies and five eQTL studies were referenced in this paper. We found several candidate SNPs that have a strong relationship with AD. Most of these SNPs overlap in different data sets, providing relatively strong reliability. We also explain the function of the novel AD-related genes we have discovered.
阿尔茨海默病（AD）是继癌症、心脏病和脑血管疾病之后老年人死亡的第四大主要原因。寻找候选致病基因有助于设计基因靶向药物，并有效降低疾病风险。像AD这样的复杂疾病通常由多个基因引起。全基因组关联研究（GWAS）已经确定了大多数疾病的潜在基因变异。然而，由于连锁不平衡（LD），很难识别直接导致疾病的致病突变。在本研究中，我们将表达定量性状位点（eQTL）研究与GWAS相结合，以全面定义导致阿尔茨海默病的基因。所使用的方法是汇总孟德尔随机化（SMR），这是一种整合汇总数据的新方法。本文参考了两项GWAS研究和五项eQTL研究。我们发现了几个与AD有密切关系的候选单核苷酸多态性（SNP）。这些SNP中的大多数在不同的数据集中重叠，提供了相对较强的可靠性。我们还解释了我们发现的新型AD相关基因的功能。
