Detection of inappropriate samples in association studies by an IBS-based method considering linkage disequilibrium between genetic markers
Detection of inappropriate samples in association studies by an IBS-based method considering linkage disequilibrium between genetic markers
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DOI：
10.1038/jhg.2010.43
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发表时间：
2010-07-01
影响因子：
3.5
通讯作者：
Ohtaki, Megu
中科院分区：
文献类型：
--
作者：
Andoh, Masataka;Sato, Yasunori;Ohtaki, Megu
关联研究是一种流行的研究设计，用于识别常见复杂疾病的易感基因。在这样的研究中，存在不适当的样本，例如来自近亲或显示DNA污染的样本，会导致I型错误的膨胀或功效的降低。在这里，我们提出了一个身份的状态（IBS）为基础的检测方法，不适当的样本考虑连锁不平衡（LD）。检验统计量是在关联研究中每个样本对之间在每个单核苷酸多态性（SNP）处由州共享相同的等位基因的比例的平均值。引入两个SNP之间共享等位基因数目的协方差来考虑LD。我们表明，在计算机模拟数据中可以准确估计第一类错误和功效，并且如果分析的SNP数量较少，则在模拟LD中检测不适当样本的性能优于之前的方法，并且具有上级性能。应用到真实的关联研究数据表明，如果LD被认为是在估计分布的检验统计量的准确性提高。检测到被认为是同胞的样品对。这些结果表明，LD考虑IBS为基础的检测方法是有用的，在关联研究中识别不适当的样本。Journal of Human Genetics（2010）55，436-440; doi：10.1038/jhg.2010.43; 2010年5月7日在线发表
An association study is a popular study design to identify susceptibility genes for common complex diseases. In such a study, the presence of inappropriate samples, such as those derived from close relatives or showing DNA contamination, causes an inflation of type I error or a decrease of power. Here we propose an identity-by-state (IBS)-based detection method of inappropriate samples taking linkage disequilibrium (LD) into consideration. The test statistics is the mean of the proportion of alleles that are shared identical by state at each single nucleotide polymorphism (SNP) between each sample pair in an association study. A covariance of the number of shared alleles between two SNPs is introduced to consider LD. We show that type I error and power are estimated accurately in computer-simulated data, and that if the number of SNPs analyzed is small, the performance of detection of inappropriate samples is superior to the previous method in simulated LD. An application to real association study data showed that accuracy in estimating the distribution of test statistics improved if LD was considered. Sample pairs considered to be siblings were detected. These results suggested that an LD-considered IBS-based detection method is useful in identifying inappropriate samples in an association study. Journal of Human Genetics (2010) 55, 436-440; doi:10.1038/jhg.2010.43; published online 7 May 2010