SNPing away at complex diseases:: Analysis of single-nucleotide polymorphisms around APOE in Alzheimer disease
SNPing away at complex diseases:: Analysis of single-nucleotide polymorphisms around APOE in Alzheimer disease
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DOI：
10.1086/303003
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发表时间：
2000-08-01
影响因子：
9.8
通讯作者：
Vance, JM
中科院分区：
文献类型：
--
作者：
Martin, ER;Lai, EH;Vance, JM
人们对使用单核苷酸多态性（SNPs）寻找复杂疾病基因的前景产生了极大的兴趣，目前正在进行几项致力于在整个人类基因组中识别和绘制SNPs的计划。然而，调查使用SNP识别复杂疾病基因的实际数据很少。为了开始研究在复杂疾病研究中使用SNP的相关问题，我们围绕晚发性阿尔茨海默病（AD）的公认易感基因APOE启动了一项协作SNP作图研究。60个单核苷酸多态性在1.5 Mb区域周围的载脂蛋白E基因型无关的AD病例，在控制，并在AD家族的样本。在病例和对照中进行标准测试以寻找SNP等位基因与AD的关联。我们还使用了基于家族的关联分析，包括最近开发的方法来寻找单倍型关联。13个SNPs中有7个（包括APOE-4多态性，在APOE两侧跨越40 kb）有关联证据（P小于或等于0.05）。正如预期的那样，APOE-4多态性和其他两个SNP与AD相关的证据非常有力，
There has been great interest in the prospects of using single-nucleotide polymorphisms (SNPs) in the search for complex disease genes, and several initiatives devoted to the identification and mapping of SNPs throughout the human genome are currently underway. However, actual data investigating the use of SNPs for identification of complex disease genes are scarce. To begin to look at issues surrounding the use of SNPs in complex disease studies, we have initiated a collaborative SNP mapping study around APOE, the well-established susceptibility gene for late-onset Alzheimer disease (AD). Sixty SNPs in a 1.5-Mb region surrounding APOE were genotyped in samples of unrelated cases of AD, in controls, and in families with AD. Standard tests were conducted to look for association of SNP alleles with AD, in cases and controls. We also used family-based association analyses, including recently developed methods to look for haplotype association. Evidence of association (P less than or equal to .05) was identified for 7 of 13 SNPs, including the APOE-4 polymorphism, spanning 40 kb on either side of APOE. As expected, very strong evidence for association with AD was seen for the APOE-4 polymorphism, as well as for two other SNPs that lie