Oncotarget

Research Papers: Gerotarget (Focus on Aging):

Risk prediction for sporadic Alzheimer’s disease using genetic risk score in the Han Chinese population

Qianyi Xiao, Zhi-Jun Liu, Sha Tao, Yi-Min Sun, Deke Jiang, Hong-Lei Li, Haitao Chen, Xu Liu, Brittany Lapin, Chi-Hsiung Wang, S. Lilly Zheng, Jianfeng Xu and Zhi-Ying Wu _

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Oncotarget. 2015; 6:36955-36964. https://doi.org/10.18632/oncotarget.6271

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Abstract

Qianyi Xiao1,*, Zhi-Jun Liu2,3,*, Sha Tao1,*, Yi-Min Sun3, Deke Jiang4, Hong-Lei Li2, Haitao Chen1, Xu Liu4, Brittany Lapin5, Chi-Hsiung Wang5, S. Lilly Zheng4,5, Jianfeng Xu1,4,5,6,* and Zhi-Ying Wu2,*

1 Center for Genomic Translational Medicine and Prevention, School of Public Health, Fudan University, Shanghai, China

2 Department of Neurology and Research Center of Neurology in Second Affiliated Hospital, and the Collaborative Innovation Center for Brain Science, Zhejiang University School of Medicine, Hangzhou, China

3 Department of Neurology and Institute of Neurology, Huashan Hospital, Fudan University, Shanghai, China

4 State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China

5 Program for Personalized Cancer Care, NorthShore University Health System, Evanston, IL, USA

6 Fudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai, China

* These authors have contributed equally to this work

Correspondence to:

Zhi-Ying Wu, email:

Jianfeng Xu, email:

Keywords: Alzheimer’s disease, genetic risk score, risk prediction, single nucleotide polymorphism, association, Gerotarget

Received: September 10, 2015 Accepted: September 22, 2015 Published: November 02, 2015

Abstract

More than 30 independent single-nucleotide polymorphisms (SNPs) have been associated with Alzheimer’s disease (AD) risk by genome-wide association studies (GWAS) in European. We aimed to confirm these SNPs in Chinese Han and investigate the utility of these genetic markers. We randomly divided 459 sporadic AD (SAD) patients and 751 cognitively normal controls into two sets (discovery and testing). Thirty-three SAD risk-associated SNPs were firstly tested in the discovery set. Significant SNPs were used to calculate genetic risk score (GRS) in the testing set. Predictive performance of GRS was evaluated using the area under the receiver operating characteristic curve (AUC). In the discovery set, 6 SNPs were confirmed (P = 7.87x10-11~0.048), including rs9349407 in CD2AP, rs11218343 in SORL1, rs17125944 in FERMT2, rs6859 in PVRL2, rs157580 and rs2075650 in TOMM40. The first three SNPs were associated with SAD risk independent of APOE genotypes. GRS based on these three SNPs were significantly associated with SAD risk in the independent testing set (P = 0.002). The AUC for discriminating cases from controls was 0.58 for GRS, 0.60 for APOE, and 0.64 for GRS and APOE. Our data demonstrated that GRS based on AD risk-associated SNPs may supplement APOE for better assessing individual risk for AD in Chinese.


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