X-chromosome genetic association test incorporating X-chromosome inactivation and imprinting effects

Abstract

Studies have shown that many complex diseases are sex-determined. When conducting genetic association studies on X-chromosome, 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 MLRXCII. Extensive simulation studies are carried out to investigate the type I error rate and the test power of the proposed MLRXCII. Simulation results demonstrate that the proposed test controls the type I error rate well and is more powerful than the existing method when imprinting effects exist. The proposed MLRXCII test is valid and powerful in genetic association studies on X-chromosome for qualitative traits and thus is recommended in practice.