The associations of APP, PSEN1, and PSEN2 genes with Alzheimer's disease: A large case–control study in Chinese population. (10th October 2022)

• Record Type: Journal Article
• Authors: Xiao, Xuewen; Liu, Hui; Zhou, Lu; Liu, Xixi; Xu, Tianyan; Zhu, Yuan; Yang, Qijie; Hao, Xiaoli; Liu, Yingzi; Zhang, Weiwei; Zhou, Yafang; Wang, Junling; Li, Jinchen; Jiao, Bin; Shen, Lu; Liao, Xinxin
• Is Part Of: CNS neuroscience & therapeutics. Volume 29:Number 1(2023)
• Page Start: 122
• Page End: 128
• Publication Date: 2022-10-10
• Subjects: Alzheimer's disease -- APP -- PSEN1 -- PSEN2 -- the Chinese population; Neuropharmacology -- Periodicals; Central nervous system -- Diseases -- Effect of drugs on -- Periodicals; 612.8
• DOI: 10.1111/cns.13987
• Languages: English
• ISSNs: 1755-5930

Abstract

Abstract: Aim: The associations of non‐pathogenic variants of APP, PSEN1, and PSEN2 with Alzheimer's disease (AD) remain unclear. This study is aimed at determining the role of these variants in AD. Methods: Our study recruited 1154 AD patients and 2403 controls. APP, PSEN1, PSEN2, and APOE were sequenced using a targeted panel. Variants were classified into common or rare variants with the minor allele frequencies (MAF) cutoff of 0.01. Common variant (MAF≥0.01)‐based association test was performed by PLINK 1.9, and gene‐based (MAF <0.01) association analysis was conducted using Sequence Kernel Association Test‐Optimal (SKAT‐O test). Additionally, using PLINK 1.9, we performed AD endophenotypes association studies. Results: A common variant, PSEN2 rs11405, was suggestively associated with AD risk ( p = 1.08 × 10 −2 ). The gene‐based association analysis revealed that the APP gene exhibited a significant association with AD ( p = 1.43 × 10 −2 ). In the AD endophenotypes association studies, APP rs459543 was nominally correlated with CSF Aβ42 level ( p = 7.91 × 10 −3 ). Conclusion: Our study indicated that non‐pathogenic variants in PSEN2 and APP may be involved in AD pathogenesis in the Chinese population. Abstract : In this study, we systematically explored the relationship between Alzheimer's disease (AD) and non‐pathogenic variants of APP, PSEN1, and PSEN2 in a total of 3557 individuals in a Chinese population. The common variant association test revealed that PSEN2 rs11405 were nominally associated with AD. Gene‐based association analysis indicated that non‐pathogenic variants in APP gene may contribute to the etiology of AD. Our study indicated that non‐pathogenic variants in PSEN2 and APP may be involved in AD pathogenesis in the Chinese population.