Impact of Non-Ignorable Missingness on Genetic Tests of Linkage and/or Association Using Case-Parent Trios

Abstract

The transmission/disequilibrium test was introduced to test for linkage disequilibrium between a marker and a putative disease locus using case-parent trios. However, parental genotypes may be incomplete in such a study. When parental information is non-randomly missing, due, for example, to death from the disease under study, the impact on type I error and power under dominant and recessive disease models has been reported. In this paper, we examine non-ignorable missingness by assigning missing values to the genotypes of affected parents. We used unrelated case-parent trios in the Genetic Analysis Workshop 14 simulated data for the Danacaa population. Our computer simulations revealed that the type I error of these tests using incomplete trios was not inflated over the nominal level under either recessive or dominant disease models. However, the power of these tests appears to be inflated over the complete information case due to an excess of heterozygous parents in dyads.