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New insights into old methods for identifying causal rare variants

机译:对识别因果稀有变异的旧方法的新见解

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The advance of high-throughput next-generation sequencing technology makes possible the analysis of rare variants. However, the investigation of rare variants in unrelated-individuals data sets faces the challenge of low power, and most methods circumvent the difficulty by using various collapsing procedures based on genes, pathways, or gene clusters. We suggest a new way to identify causal rare variants using the F -statistic and sliced inverse regression. The procedure is tested on the data set provided by the Genetic Analysis Workshop 17 (GAW17). After preliminary data reduction, we ranked markers according to their F -statistic values. Top-ranked markers were then subjected to sliced inverse regression, and those with higher absolute coefficients in the most significant sliced inverse regression direction were selected. The procedure yields good false discovery rates for the GAW17 data and thus is a promising method for future study on rare variants.
机译:高通量下一代测序技术的进步使稀有变异的分析成为可能。但是,对无关个人数据集中的稀有变种进行研究面临着低功耗的挑战,并且大多数方法通过使用基于基因,途径或基因簇的各种折叠程序来规避这一难题。我们建议使用F统计量和切片逆回归来识别因果稀有变异的新方法。该程序在遗传分析研讨会17(GAW17)提供的数据集上进行了测试。在初步数据精简之后,我们根据标记的F统计值对标记进行排名。然后对排名最高的标记进行切片逆回归,并选择在最显着的切片逆回归方向上具有较高绝对系数的标记。该程序为GAW17数据提供了良好的错误发现率,因此是将来对稀有变体进行研究的有前途的方法。

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