人类X染色体失活是指女性胚胎发育早期两条X染色体中只表达其中一条以保证X连锁基因在两性间达到剂量平衡的现象，其还涉及基因组印记。研究表明，很多遗传病的发病机理跟X连锁基因失活及印记效应密切相关。目前，虽然已有一些关联分析方法研究X染色体失活对X伴性遗传病的影响，但均未合并印记效应的信息，这与X染色体的遗传机制不符，存在以下尚未解决的重要问题与难题：如何用统计指标度量X染色体失活的程度？基于加性遗传模型，如何将X染色体失活与印记效应合并到X染色体上的关联分析之中以提高其检验效能？如何建立对遗传模型不做限制的合并X染色体失活与印记效应的关联分析方法？因此，本项目将建立度量X染色体失活程度的统计指标；提出基于加性模型合并X染色体失活与印记效应的关联分析方法；建立对各种遗传模型均比较稳健的合并X染色体失活与印记效应的关联分析方法，为遗传流行病学中更加精准地定位X连锁基因提供理论支持和有效统计工具。

X chromosome inactivation (XCI) is the phenomenon that only one of two copies of X chromosome in females, during early embryonic development, is expressed to achieve the dose compensation of X-linked genes between males and females, which is stated to be related to genomic imprinting. It has been shown in literature that the genetic mechanism of many complex diseases is associated with the inactivated X-linked genes and imprinting effects. Currently, there have been several studies which incorporate the XCI into association analysis. However, they do not take account of imprinting effects, which is not matched with the inheritance of X chromosome. Nowadays, there are still the following unsolved but important issues and challenges. First, how to measure the degree of XCI and how to estimate this measure? Second, based on the additive genetic model, how to incorporate both the XCI and genetic imprinting into association study on X chromosome to improve the test power? Third, for the model-free case, how to develop the X-chromosome association study with the XCI and genetic imprinting? Therefore, in this project, we will first find a statistical method to estimate the degree of the XCI. Next, based on the additive genetic model, we will take account of the XCI and imprinting and propose a method to test for association between the genes on X chromosome and the diseases. Finally, we will suggest a method to detect the X-chromosome association by accounting for the XCI and imprinting, which is robust to various genetic models. To this connection, the issues considered in this project would provide both theoretical support and useful statistical tools for fine mapping on X chromosome.