Genetic risk score modifies the effect of APOE on risk and age onset of Alzheimer's disease

被引：4

作者：

Shi, Zhuqing ^{[1
,2
,3
]}

Yu, Hongjie ^{[3
]}

Wu, Yishuo ^{[3
,4
]}

Ford, Madison ^{[3
]}

Perschon, Chelsea ^{[3
]}

Wang, Chihsiung ^{[5
]}

Zheng, Siqun L. ^{[3
]}

Xu, Jianfeng ^{[1
,2
,3
,4
]}

机构：

[1] Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Shanghai, Peoples R China

[2] Fudan Univ, Sch Life Sci, Ctr Genet Epidemiol, Shanghai, Peoples R China

[3] NorthShore Univ HealthSyst, Program Personalized Canc Care, 1001 Univ Pl, Evanston, IL 60201 USA

[4] Fudan Univ, Fudan Inst Urol, Huashan Hosp, Shanghai, Peoples R China

[5] NorthShore Univ Hlth Syst, Ctr Biomed Res Informat, Evanston, IL USA

来源：

CLINICAL GENETICS | 2019年 / 95卷 / 02期

关键词：

Alzheimer's disease; APOE; case-control studies; genetic risk score; single nucleotide polymorphism; HAN CHINESE; COMMON VARIANTS; PREDICTION; BREAST; LOCI; ASSOCIATION; DECLINE; CD2AP; EPHA1; CD33;

D O I：

10.1111/cge.13479

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Single nucleotide polymorphism (SNP)-based genetic risk score (GRS) and APOE genotype are both important in risk prediction of Alzheimer's disease (AD); however, the interaction between GRS and APOE has not been extensively investigated. Our objective was to determine whether GRS modifies the APOE effect on AD risk and age at onset (AAO). The study included 774 AD cases and 767 controls of European descent. Population standardized GRS was calculated based on 17 previously implicated AD risk-associated SNPs. Association was analyzed using logistic regression, Cox proportional hazards model and Kaplan-Meier curve. We found that GRS was significantly associated with AD risk and the association was stronger among APOE epsilon 4 carriers. Compared to epsilon 4 non-carriers, the Odds Ratio (OR) for AD was 8.09 (95% Confidence Interval [CI]: 4.98-13.63) for epsilon 4 carriers with high-GRS (>= 1.5). In contrast, the OR was 2.55 (95% CI: 1.46-4.49) for epsilon 4 carriers with low-GRS (<0.6). In conclusion, these results suggest SNP-based GRS may supplement APOE for better assessment of inherited risk and age of onset of AD.

引用

页码：302 / 309

页数：8

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