A robust test for X-chromosome genetic association accounting for X-chromosome inactivation and imprinting
A robust test for X-chromosome genetic association accounting for X-chromosome inactivation and imprinting
复制标题
解释 X 染色体失活和印记的 X 染色体遗传关联的稳健测试
DOI：
10.1017/s0016672320000026
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发表时间：
2020-01-01
影响因子：
1.5
通讯作者：
Zhou，Ji-Yuan
中科院分区：
文献类型：
--
作者：
Zhang，Yu;Xu，Si-Qi;Zhou，Ji-Yuan
众所周知，X染色体在许多性别特有的疾病中起着重要作用。然而，只有X染色体上的少数单核苷酸多态被发现与疾病相关。与常染色体相比，对X染色体进行关联测试更加困难，因为女性和男性的X染色体数量不同。另一方面，X染色体失活发生在雌性哺乳动物身上，这是一种在雌性哺乳动物中，为了达到与雄性相同的基因表达水平，两条X染色体中的一个拷贝的表达被沉默的现象。此外，印记效应可能与某些疾病有关。目前，有一些现有的方法在测试X染色体上的关联性时考虑到X染色体的失活。但是，它们都不允许产生印记效果。因此，在本文中，我们提出了一种稳健的检验，ZXCII，它同时考虑了X染色体的失活和印记效应，而不需要事先指定遗传模型。为了考察ZXCII在不同参数值的各种场景下的有效性和性能，进行了仿真研究。仿真结果表明，在不存在关联的情况下，ZXCII能够很好地控制I类误码率。此外，在功率方面，ZXCII在所考虑的所有情况下都是健壮的，并且在存在印记效果的情况下，特别是在完全印记效果的情况下，通常优于大多数现有的方法。
The X chromosome is known to play an important role in many sex-specific diseases. However, only a few single-nucleotide polymorphisms on the X chromosome have been found to be associated with diseases. Compared to the autosomes, conducting association tests on the X chromosome is more intractable due to the difference in the number of X chromosomes between females and males. On the other hand, X-chromosome inactivation takes place in female mammals, which is a phenomenon in which the expression of one copy of two X chromosomes in females is silenced in order to achieve the same gene expression level as that in males. In addition, imprinting effects may be related to certain diseases. Currently, there are some existing approaches taking X-chromosome inactivation into account when testing for associations on the X chromosome. However, none of them allows for imprinting effects. Therefore, in this paper, we propose a robust test, ZXCII, which accounts for both X-chromosome inactivation and imprinting effects without requiring specifying the genetic models in advance. Simulation studies are conducted in order to investigate the validity and performance of ZXCII under various scenarios of different parameter values. The simulation results show that ZXCII controls the type I error rate well when there is no association. Furthermore, with regards to power, ZXCII is robust in all of the situations considered and generally outperforms most of the existing methods in the presence of imprinting effects, especially under complete imprinting effects.