Division of Biostatistics, Institute of Public Health, National Yang Ming University, Taipei, Taiwan, ROC.
J Hum Genet. 2012 Sep;57(9):601-9. doi: 10.1038/jhg.2012.78. Epub 2012 Jun 28.
In general, multiple issues are examined before the analysis of genetic data such as Hardy-Weinberg Equilibrium and Mendelian errors. Although missing genotypes are commonly observed in genetic studies, potential bias due to informative missingness is usually overlooked. Therefore, the Test of Informative Missingness (TIM) was the first attempt to determine whether or not parental genotypes are missing informatively. The TIM is a useful tool for genetic data cleaning. For example, excluding single-nucleotide polymorphisms that appear to be missing informatively may further improve the quality of genetic data. Although the TIM has decent power, its performance is discernibly weaker when the minor allele/genotype introduces informative missingness. In an effort to avoid such reduced power, the newly proposed strategy detects informative missingness by comparing inconsistent linkage disequilibrium signals between intact case-parent triads and incomplete data. Computer simulations revealed that the new method was robust to population stratifications and more powerful than the TIM in most situations. In addition, the new method demonstrated decent power in the genome-wide association study, even if the most conservative correction for multiple testing was adopted.
通常，在分析遗传数据（如 Hardy-Weinberg 平衡和 Mendelian 错误）之前，会检查多个问题。尽管在遗传研究中经常观察到缺失基因型，但由于信息缺失导致的潜在偏差通常被忽视。因此，信息缺失检验（TIM）是首次尝试确定父母基因型是否存在信息缺失的方法。TIM 是一种用于遗传数据清理的有用工具。例如，排除似乎存在信息缺失的单核苷酸多态性可能会进一步提高遗传数据的质量。尽管 TIM 具有相当的功效，但当次要等位基因/基因型引入信息缺失时，其性能明显减弱。为了避免这种功效降低，新提出的策略通过比较完整病例-父母三体型和不完整数据之间不一致的连锁不平衡信号来检测信息缺失。计算机模拟表明，该新方法对群体分层具有稳健性，并且在大多数情况下比 TIM 更有效。此外，即使采用最保守的多重检验校正，该新方法在全基因组关联研究中也具有良好的功效。
