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Power and type I error rate of false discovery rate approaches in genome-wide association studies

机译:全基因组关联研究中错误发现率方法的功效和I型错误率

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摘要

In genome-wide genetic studies with a large number of markers, balancing the type I error rate and power is a challenging issue. Recently proposed false discovery rate (FDR) approaches are promising solutions to this problem. Using the 100 simulated datasets of a genome-wide marker map spaced about 3 cM and phenotypes from the Genetic Analysis Workshop 14, we studied the type I error rate and power of Storey's FDR approach, and compared it to the traditional Bonferroni procedure. We confirmed that Storey's FDR approach had a strong control of FDR. We found that Storey's FDR approach only provided weak control of family-wise error rate (FWER). For these simulated datasets, Storey's FDR approach only had slightly higher power than the Bonferroni procedure. In conclusion, Storey's FDR approach is more powerful than the Bonferroni procedure if strong control of FDR or weak control of FWER is desired. Storey's FDR approach has little power advantage over the Bonferroni procedure if there is low linkage disequilibrium among the markers. Further evaluation of the type I error rate and power of the FDR approaches for higher linkage disequilibrium and for haplotype analyses is warranted.
机译:在具有大量标记的全基因组遗传研究中,平衡I型错误率和功效是一个具有挑战性的问题。最近提出的错误发现率(FDR)方法是解决该问题的有前途的解决方案。使用来自遗传分析研讨会14的约3 cM和表型的全基因组标记图的100个模拟数据集,我们研究了Storey FDR方法的I型错误率和功效,并将其与传统的Bonferroni方法进行了比较。我们确认Storey的FDR方法对FDR具有强大的控制力。我们发现Storey的FDR方法仅提供了对家庭错误率(FWER)的弱控制。对于这些模拟的数据集,Storey的FDR方法仅具有比Bonferroni过程稍高的功效。总之,如果需要对FDR进行严格控制或对FWER进行较弱控制,则Storey的FDR方法比Bonferroni程序更强大。如果标记之间的连锁不平衡程度较低,那么Storey的FDR方法与Bonferroni程序相比几乎没有力量优势。对于更高的连锁不平衡和单倍型分析,有必要进一步评估I型错误率和FDR方法的功效。

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