Dataset Information

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

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.

SUBMITTER: Zhou X

PROVIDER: S-EPMC7403835 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Zhou Xiaopu X Chen Yu Y Ip Fanny C F FCF Lai Nicole C H NCH Li Yolanda Y T YYT Jiang Yuanbing Y Zhong Huan H Chen Yuewen Y Zhang Yulin Y Ma Shuangshuang S Lo Ronnie M N RMN Cheung Kit K Tong Estella P S EPS Ko Ho H Shoai Maryam M Mok Kin Y KY Hardy John J Mok Vincent C T VCT Kwok Timothy C Y TCY Fu Amy K Y AKY Ip Nancy Y NY

Alzheimer's & dementia (Amsterdam, Netherlands) 20200805 1

<h4>Introduction</h4>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.<h4>Methods</h4>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 polyge ...[more]

PMID: 32775599

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Project description:The heritability of Alzheimer's disease estimated from twin studies is greater than the heritability derived from genome-based studies, for reasons that remain unclear. We apply both approaches to the same twin sample, considering both Alzheimer's disease polygenic risk scores and heritability from twin models, to provide insight into the role of measured genetic variants and to quantify uncaptured genetic risk. A population-based heritability and polygenic association study of Alzheimer's disease was conducted between 1986 and 2016 and is the first study to incorporate polygenic risk scores into biometrical twin models of Alzheimer's disease. The sample included 1586 twins drawn from the Swedish Twin Registry which were nested within 1137 twin pairs (449 complete pairs and 688 incomplete pairs) with clinically based diagnoses and registry follow-up (M age = 85.28, SD = 7.02; 44% male; 431 cases and 1155 controls). We report contributions of polygenic risk scores at P < 1 × 10-5, considering a full polygenic risk score (PRS), PRS without the APOE region (PRS.no.APOE) and PRS.no.APOE plus directly measured APOE alleles. Biometric twin models estimated the contribution of environmental influences and measured (PRS) and unmeasured genes to Alzheimer's disease risk. The full PRS and PRS.no.APOE contributed 10.1 and 2.4% to Alzheimer's disease risk, respectively. When APOE ɛ4 alleles were added to the model with the PRS.no.APOE, the total contribution was 11.4% to Alzheimer's disease risk, where APOE ɛ4 explained 9.3% and PRS.no.APOE dropped from 2.4 to 2.1%. The total genetic contribution to Alzheimer's disease risk, measured and unmeasured, was 71% while environmental influences unique to each twin accounted for 29% of the risk. The APOE region accounts for much of the measurable genetic contribution to Alzheimer's disease, with a smaller contribution from other measured polygenic influences. Importantly, substantial background genetic influences remain to be understood.

Dataset Information

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

Publications

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

Similar Datasets

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