A Comparison of Association Statistics between Pooled and Individual Genotypes
A Comparison of Association Statistics between Pooled and Individual Genotypes
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DOI：
10.1159/000194975
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发表时间：
2009-01-01
期刊：
影响因子：
1.8
通讯作者：
Rice, John P.
中科院分区：
文献类型：
--
作者：
Knight, Jo;Saccone, Scott F.;Rice, John P.
背景：个体基因分型的标记物可以通过对混合DNA进行定量基因分型来选择。这种策略节省了时间和金钱。研究方法：为了确定这种方法的有效性，我们研究了来自合并和个体基因型的关联检验统计量的二元分布。我们使用了大约1,000个样本，对40,000个SNP进行了单独和合并的基因分型。结果与结论：我们发现，联合检验统计量的分布可以建模为两个二元正态分布的混合。一个分布的相关性为零，这可能是由于合并基因分型不成功的SNP。在我们的数据中，另一个分布的相关性约为0.65。后一种分布可能是由SNP解释的，其合并的基因分型准确地预测了潜在的等位基因频率。大约87%的数据属于这种分布。我们还推导出一种方法来研究相关性和选择截止值对合并研究相对功效的影响。我们证明，合并基因分型有很好的权力，以检测SNP是真正相关的致病变异的SNP显示出良好的相关性之间的合并和个人的基因分型。因此，这种方法是一种成本效益高的关联研究工具。版权所有（C）2009 S. Karger AG，巴塞尔
Background: Markers for individual genotyping can be selected using quantitative genotyping of pooled DNA. This strategy saves time and money. Methods: To determine the efficacy of this approach, we investigated the bivariate distribution of association test statistics from pooled and individual genotypes. We used a sample of approximately 1,000 samples with individual and pooled genotyping on 40,000 SNPs. Results and Conclusions: We found that the distribution of the joint test statistics can be modelled as a mixture of two bivariate normal distributions. One distribution has a correlation of zero, and is probably due to SNPs whose pooled genotyping was unsuccessful. The other distribution has a correlation of approximately 0.65 in our data. This latter distribution is probably accounted for by SNPs whose pooled genotyping accurately predicts the underlying allele frequency. Approximately 87% of the data belongs to this distribution. We also derived a method to investigate the effect of both the correlation and selection cut-off on the relative power of pooling studies. We demonstrate that pooled genotyping has good power to detect SNPs that are truly associated with disease-causing variants for SNPs showing good correlation between pooled and individual genotyping. Therefore, this approach is a cost effective tool for association studies. Copyright (C) 2009 S. Karger AG, Basel