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 andis 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.

中文翻译：

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X染色体遗传关联测试结合了X染色体的失活和印迹效应。

研究表明，许多复杂的疾病是由性别决定的。在对X染色体进行遗传关联研究时，应同时考虑两个重要的表观遗传因素：X染色体失活和基因组印迹。当前，已经有几种关联测试说明了X染色体失活的信息。但是，这些测试没有考虑压印效果。在本文中，我们提出了一种新颖的关联测试，该测试同时针对雌性后代和亲本后代，并结合男性后代的病例对照数据，以MLRXCII表示，同时结合了X染色体失活和印迹效应。进行了广泛的仿真研究，以研究所提出的MLRXCII的I型错误率和测试能力。仿真结果表明，所提出的测试能够很好地控制I类错误率，并且在存在压印效果时比现有方法具有更强大的功能。所提出的MLRXCII测试在X染色体定性性状的遗传关联研究中是有效的，因此在实践中值得推荐。