Genetic and polygenic risk score analysis for Alzheimer's disease in the Chinese population

• Main Authors: Xiaopu Zhou, Yu Chen, Fanny C. F. Ip, Nicole C. H. Lai, Yolanda Y. T. Li, Yuanbing Jiang, Huan Zhong, Yuewen Chen, Yulin Zhang, Shuangshuang Ma, Ronnie M. N. Lo, Kit Cheung, Estella P. S. Tong, Ho Ko, Maryam Shoai, Kin Y. Mok, John Hardy, Vincent C. T. Mok, Timothy C. Y. Kwok, Amy K. Y. Fu, Nancy Y. Ip
• Format: Article
• Language: English
• Published: Wiley 2020-01-01
• Series: Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring
• Subjects: Alzheimer's disease; disease risk; polygenic risk score; population genetics; SORL1
• Online Access: https://doi.org/10.1002/dad2.12074
• ISSN: 2352-8729

Abstract Introduction Dozens of Alzheimer's disease (AD)‐associated loci have been identified in European‐descent populations, but their effects have not been thoroughly investigated in the Hong Kong Chinese population. Methods TaqMan array genotyping was performed for known AD‐associated variants in a Hong Kong Chinese cohort. Regression analysis was conducted to study the associations of variants with AD‐associated traits and biomarkers. Lasso regression was applied to establish a polygenic risk score (PRS) model for AD risk prediction. Results SORL1 is associated with AD in the Hong Kong Chinese population. Meta‐analysis corroborates the AD‐protective effect of the SORL1 rs11218343 C allele. The PRS is developed and associated with AD risk, cognitive status, and AD‐related endophenotypes. TREM2 H157Y might influence the amyloid beta 42/40 ratio and levels of immune‐associated proteins in plasma. Discussion SORL1 is associated with AD in the Hong Kong Chinese population. The PRS model can predict AD risk and cognitive status in this population.