Won Sungho, Lange Christoph
Department of Applied Statistics, Chung-Ang University, Seoul, Korea.
Stat Med. 2013 Nov 10;32(25):4482-98. doi: 10.1002/sim.5865. Epub 2013 Jun 6.
Although transmission disequilibrium tests (TDT) and the FBAT statistic are robust against population substructure, they have reduced statistical power, as compared with fully efficient tests that are not guarded against confounding because of population substructure. This has often limited the application of transmission disequilibrium tests/FBATs to candidate gene analysis, because, in a genome-wide association study, population substructure can be adjusted by approaches such as genomic control and EIGENSTRAT. Here, we provide new statistical methods for the analysis of quantitative and dichotomous phenotypes in extended families. Although the approach utilizes the polygenic model to maximize the efficiency, it still preserves the robustness to non-normality and misspecified covariance structures. In addition, the proposed method performs better than the existing methods for dichotomous phenotype, and the new transmission disequilibrium test for candidate gene analysis is more efficient than FBAT statistics.
尽管传递不平衡检验（TDT）和FBAT统计量对群体亚结构具有稳健性，但与未针对群体亚结构导致的混杂因素进行防范的完全高效检验相比，它们的统计功效有所降低。这常常限制了传递不平衡检验/FBAT在候选基因分析中的应用，因为在全基因组关联研究中，群体亚结构可以通过诸如基因组控制和EIGENSTRAT等方法进行调整。在此，我们提供了用于分析大家庭中定量和二分表型的新统计方法。尽管该方法利用多基因模型来最大化效率，但它仍然保持了对非正态性和错误指定的协方差结构的稳健性。此外，所提出的方法在二分表型方面比现有方法表现更好，并且用于候选基因分析的新传递不平衡检验比FBAT统计量更有效。
