Tyrer Jonathan, Pharoah Paul D P, Easton Douglas F
Strangeways Research Laboratory, Department of Oncology, University of Cambridge, Worts Causeway, Cambridge, UK.
Genet Epidemiol. 2006 Nov;30(7):636-43. doi: 10.1002/gepi.20175.
Disease association studies often test large numbers of markers, and various methods have been proposed to correct for multiple testing. In this paper, we propose an admixture maximum likelihood approach that estimates both the proportion of associated single nucleotide polymorphisms (SNPs) and their typical effect size. We assessed this method and compared it with several previously proposed approaches by simulation. The maximum likelihood approach performed similarly to or better than all other tests across a wide range of alternative hypotheses. The rank truncated product method also had good power, though somewhat inferior to the maximum likelihood approach in most cases. A simple Bonferroni correction performed best only when the number of associated SNPs was small.
疾病关联研究通常会测试大量标记,并且已经提出了各种方法来校正多重检验。在本文中,我们提出了一种混合最大似然方法,该方法可以估计相关单核苷酸多态性(SNP)的比例及其典型效应大小。我们评估了该方法,并通过模拟将其与几种先前提出的方法进行了比较。在广泛的备择假设下,最大似然方法的表现与所有其他检验相似或更好。秩截断乘积法也具有良好的检验效能,尽管在大多数情况下略逊于最大似然方法。简单的Bonferroni校正仅在相关SNP数量较少时表现最佳。