The Associations of APP, PSEN1, and PSEN2 Genes with Alzheimer's Disease: A Large Case-Control Study in Chinese Population

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 x 10(-2)). The gene-based association analysis revealed that the APP gene exhibited a significant association with AD (p = 1.43 x 10(-2)). In the AD endophenotypes association studies, APP rs459543 was nominally correlated with CSF A beta 42 level (p = 7.91 x 10(-3)). Conclusion Our study indicated that non-pathogenic variants in PSEN2 and APP may be involved in AD pathogenesis in the Chinese population.