Risk prediction for sporadic Alzheimer's disease using genetic risk score in the Han Chinese population.
Risk prediction for sporadic Alzheimer's disease using genetic risk score in the Han Chinese population.
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DOI：
10.18632/oncotarget.6271
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发表时间：
2015-11-10
期刊：
影响因子：
--
通讯作者：
Wu ZY
中科院分区：
文献类型：
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作者：
Xiao Q;Liu ZJ;Tao S;Sun YM;Jiang D;Li HL;Chen H;Liu X;Lapin B;Wang CH;Zheng SL;Xu J;Wu ZY
欧洲的全基因组关联研究（GWAS）发现30多个独立的单核苷酸多态性（snp）与阿尔茨海默病（AD）风险相关。我们的目的是在中国汉族中确认这些snp，并研究这些遗传标记的效用。我们将459例散发性AD （SAD）患者和751例认知正常对照随机分为两组（发现组和测试组）。首先在发现集中测试33个SAD风险相关snp。采用显著snp计算检测集中的遗传风险评分（GRS）。采用接收者工作特征曲线下面积（AUC）评价GRS的预测性能。在发现集中，共发现6个snp (P = 7.87 × 10−11~0.048)，分别为CD2AP基因rs9349407、SORL1基因rs11218343、FERMT2基因rs17125944、PVRL2基因rs6859、TOMM40基因rs157580和rs2075650。前三个snp与SAD风险相关，与APOE基因型无关。在独立测试集中，基于这三个snp的GRS与SAD风险显著相关（P = 0.002）。GRS的AUC为0.58，APOE为0.60，GRS和APOE分别为0.64。我们的数据表明，基于AD风险相关snp的GRS可以补充APOE，更好地评估中国人AD的个体风险。
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 = 7.87 × 10−11~0.048), 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.