Department of Neurology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Ph.D. Program in Translational Medicine, Kaohsiung Medical University and Academia Sinica, Kaohsiung, Taiwan.
Geriatr Gerontol Int. 2017 Nov;17(11):2184-2193. doi: 10.1111/ggi.13059. Epub 2017 Jul 4.
The general genetic background is important when studying major common diseases, such as Alzheimer's disease (AD). Determining the underlying genetic factors in populations of different races might allow for the tailored management of such diseases. The aim of the present study was to identify potential single-nucleotide polymorphisms (SNP) and genes associated with racial differences.
We identified AD-associated SNP with different carrier frequencies among races through the National Human Genome Research Institute and 1000 Genome Project databases. We generated heatmaps and carried out principle component analysis and pathway analysis. A total of 99 AD-associated SNP from genome-wide association studies were found to have different frequencies among races. Principle component analysis showed that specific SNP had higher or lower frequencies in specific races, and that similar races were clustered together.
Pathway analysis showed that a total of 15 pathways involving intracellular endocytosis, inflammation, immune response and lipid metabolism were significant, and that apolipoprotein E was involved in the most significant pathways. A literature review showed that 16 genes were involved in the pathogenesis of AD, and that the identified SNP could be used to cluster different races, suggesting that these SNP represented different genomic backgrounds of races.
As disease-associated genes might have several functional variants across different populations, these genes could be candidates for further studies, such as target gene sequencing or functional follow up of putative loci regarding racial differences. Geriatr Gerontol Int 2017; 17: 2184-2193.
在研究阿尔茨海默病（AD）等常见重大疾病时，一般遗传背景非常重要。确定不同种族人群的潜在遗传因素可能有助于此类疾病的个体化管理。本研究旨在确定与种族差异相关的潜在单核苷酸多态性（SNP）和基因。
我们通过国家人类基因组研究所和 1000 基因组计划数据库，确定了在不同种族中具有不同携带频率的 AD 相关 SNP。我们生成了热图，并进行了主成分分析和途径分析。共发现 99 个来自全基因组关联研究的 AD 相关 SNP 在不同种族中具有不同的频率。主成分分析表明，特定 SNP 在特定种族中具有更高或更低的频率，并且相似的种族聚集在一起。
途径分析表明，涉及细胞内内吞作用、炎症、免疫反应和脂质代谢的 15 条途径具有重要意义，载脂蛋白 E 参与了最重要的途径。文献综述显示，有 16 个基因参与 AD 的发病机制，所鉴定的 SNP 可用于聚类不同种族，表明这些 SNP 代表了不同种族的不同基因组背景。
由于疾病相关基因在不同人群中可能有几个功能变体，这些基因可能是进一步研究的候选基因，如针对种族差异的靶基因测序或假定基因座的功能后续研究。老年医学杂志 2017; 17: 2184-2193。
