失智症
基因
疾病
痴呆
遗传学
生物
τ蛋白
遗传关联
阿尔茨海默病
医学
单核苷酸多态性
内科学
基因型
作者
Xuewen Xiao,Zhenhua Yuan,Li-Na Guo,Xinxin Liao,Yafang Zhou,Weiwei Zhang,Lu Zhou,Xin Wang,Xixi Liu,Hui Liu,Junling Wang,Jinchen Li,Lu Shen,Bin Jiao
标识
DOI:10.1016/j.neurobiolaging.2021.05.016
摘要
• In this study, we systematically explore the relationship between FTD-associated genes and the risk of AD. • UBQLN1, MAPT, and HNRNPA1 interacted with proteins encoded by well-recognized AD-associated genes. Alzheimer's disease (AD) and frontotemporal dementia (FTD) overlap clinically and pathologically. However, the role of FTD-associated genes in patients with AD remained unclear. To explore the relationship between FTD-associated genes and AD risk, we investigated 14 FTD-associated genes via targeted next-generation sequencing panel or whole-genome sequencing in a total of 721 AD patients and 1391 controls. Common variant-based association analysis and gene-based association test of rare variants were performed by PLINK 1.9 and Sequence Kernel Association Test-Optimal (SKAT-O test) respectively. As a result, 2 common variants, UBQLN1 rs1044175 ( p value = 2.76 × 10 −4 ) and MAPT rs2258689 ( p value = 5.71 × 10 −4 ), differed significantly between AD patients and controls. Additionally, gene-based analysis aggregating rare variants demonstrated that HNRNPA1 reached statistical significance in the SKAT-O test ( p value = 2.24 × 10 −3 ). Protein–protein interaction analysis showed that UBQLN1, MAPT, and HNRNPA1 interacted with proteins encoded by well-recognized AD-associated genes. Our study indicated that UBQLN1, MAPT , and HNRNPA1 are implicated in the pathogenesis of AD in the mainland Chinese population.
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