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

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

doi:10.1002/dad2.12074

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

Alzheimers Dement (Amst). 2020 Aug 5;12(1):e12074. doi: 10.1002/dad2.12074. eCollection 2020.

Authors

Xiaopu Zhou^{1

2

3}, Yu Chen^{1

3

4}, Fanny C F Ip^{1

2

3}, Nicole C H Lai¹, Yolanda Y T Li¹, Yuanbing Jiang¹, Huan Zhong¹, Yuewen Chen^{1

3}, Yulin Zhang³, Shuangshuang Ma³, Ronnie M N Lo¹, Kit Cheung¹, Estella P S Tong¹, Ho Ko⁵, Maryam Shoai⁶, Kin Y Mok^{1

2

6}, John Hardy^{2

6

7}, Vincent C T Mok⁸, Timothy C Y Kwok⁹, Amy K Y Fu^{1

2

3}, Nancy Y Ip^{1

2

3}

Affiliations

¹ Division of Life Science State Key Laboratory of Molecular Neuroscience and Molecular Neuroscience Center The Hong Kong University of Science and Technology Clear Water Bay Kowloon Hong Kong China.
² Hong Kong Center for Neurodegenerative Diseases Hong Kong Science Park Hong Kong China.
³ Guangdong Provincial Key Laboratory of Brain Science Disease and Drug Development HKUST Shenzhen Research Institute Shenzhen-Hong Kong Institute of Brain Science Shenzhen Guangdong China.
⁴ The Brain Cognition and Brain Disease Institute Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences Shenzhen Guangdong China.
⁵ Division of Neurology Department of Medicine and Therapeutics Li Ka Shing Institute of Health Sciences School of Biomedical Sciences Gerald Choa Neuroscience Center Faculty of Medicine The Chinese University of Hong Kong Shatin Hong Kong China.
⁶ Department of Neurodegenerative Disease UCL Institute of Neurology London UK.
⁷ Institute for Advanced Study The Hong Kong University of Science and Technology Clear Water Bay Kowloon Hong Kong China.
⁸ Gerald Choa Neuroscience Centre Lui Che Woo Institute of Innovative Medicine Therese Pei Fong Chow Research Centre for Prevention of Dementia Division of Neurology Department of Medicine and Therapeutics The Chinese University of Hong Kong Shatin Hong Kong China.
⁹ Therese Pei Fong Chow Research Centre for Prevention of Dementia Division of Geriatrics Department of Medicine and Therapeutics The Chinese University of Hong Kong Shatin Hong Kong China.

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.

Keywords: Alzheimer's disease; SORL1; disease risk; polygenic risk score; population genetics.

Abstract

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