Genomic imprinting is a genetic phenomenon in which certain alleles are differentially expressed in a parent-of-origin-specific manner, and plays an important role in the study of complex traits. For a diallelic marker locus in human, the parental-asymmetry tests Q-PAT(𝑐) with any constant 𝑐 were developed to detect parent-of-origin effects for quantitative traits. However, these methods can only be applied to deal with nuclear families and thus are not suitable for extended pedigrees. In this study, by making no assumption about the distribution of the quantitative trait, we first propose the pedigree parental-asymmetry tests Q-PPAT(𝑐) with any constant 𝑐 for quantitative traits to test for parent-of-origin effects based on nuclear families with complete information from general pedigree data, in the presence of association between marker alleles under study and quantitative traits. When there are any genotypes missing in pedigrees, we utilize Monte Carlo (MC) sampling and estimation and develop the Q-MCPPAT(𝑐) statistics to test for parent-of-origin effects. Various simulation studies are conducted to assess the performance of the proposed methods, for different sample sizes, genotype missing rates, degrees of imprinting effects and population models. Simulation results show that the proposed methods control the size well under the null hypothesis of no parent-of-origin effects and Q-PPAT(𝑐) are robust to population stratification. In addition, the power comparison demonstrates that Q-PPAT(𝑐) and Q-MCPPAT(𝑐) for pedigree data are much more powerful than Q-PAT(𝑐) only using two-generation nuclear families selected from extended pedigrees.

Studies have shown that many complex diseases are sex-determined. When conducting genetic association studies on Xchromosome, there are two important epigenetic factors which should be considered simultaneously: X-chromosome inactivation and genomic imprinting. Currently, there have been several association tests accounting for the information on X-chromosome inactivation. However, these tests do not take the imprinting effects into account. In this paper, we propose a novel association test simultaneously incorporating X-chromosome inactivation and imprinting effects based on case–parent trios and control–parent trios for female offspring and case–control data for male offspring, denoted by MLR_XCII. Extensive simulation studies are carried out to investigate the type I error rate and the test power of the proposed MLR_XCII . Simulation results demonstrate that the proposed test controls the type I error rate well andis more powerful than the existing method when imprinting effects exist. The proposed MLR_XCII test is valid and powerful in genetic association studies on X-chromosome for qualitative traits and thus is recommended in practice.