A novel test of informative missingness using inconsistent linkage disequilibrium signals between case-parent triads and incomplete data

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.