Detection of Imprinting Effects for Quantitative Traits on X Chromosome Using Nuclear Families with Multiple...

Genomic imprinting is an epigenetic phenomenon in which the expression of an allele copy depends on its parental origin. This mechanism has been found to play an important role in many complex diseases. Statistical tests for imprinting effects have been developed for more than 15 years, but they are only suitable for autosomes. It was not until recently that the parental-asymmetry test on the X chromosome (XPAT) was proposed to test for imprinting effects. However, this test can only be used for qualitative traits. Therefore, in this article, we propose a class of PAT-type tests to test for imprinting for quantitative traits on the X chromosome in the presence of association, namely, Q-XPAT(c), Q-1-XPAT(c) and Q-C-XPAT(c), where c is a constant. These methods can accommodate complete and incomplete nuclear families with an arbitrary number of daughters. Extensive simulation studies demonstrate that the proposed tests control the size well under the null hypothesis of no imprinting effects and are powerful under various family structures. Moreover, by setting the inbreeding coefficient in females to be nonzero and using the assortative mating pattern in simulations, the proposed tests are shown to be valid under Hardy-Weinberg disequilibrium.