A powerful parent-of-origin effects test for qualitative traits on X chromosome in general pedigrees.
A powerful parent-of-origin effects test for qualitative traits on X chromosome in general pedigrees.
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对一般谱系中 X 染色体质量性状进行强大的亲本效应测试
DOI：
10.1186/s12859-017-2001-5
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发表时间：
2018-01-05
影响因子：
3
通讯作者：
Zhou JY
中科院分区：
文献类型：
--
作者：
Zou QL;You XP;Li JL;Fung WK;Zhou JY
基因组印迹是引起性状与基因之间关联的一种众所周知的表观遗传因素，通常通过检测等位基因的亲本起源效应来研究。基于核心家庭和一般家系，人们提出了许多方法来检测双亲起源对常染色体的影响。虽然这些对常染色体的亲本效应测试已经有15年以上的历史，但直到最近提出了X染色体亲本不对称测试（XPAT）及其扩展，才开发出用于测试X染色体亲本效应的统计测试。然而，这些X染色体的方法只适用于核心家庭，因此不适合一般家系。结果本文提出了X染色体家系亲本不对称检验（XPPAT）统计方法，用于检验存在关联的亲本起源效应，适用于一般家系。当某些家系中存在缺失基因型时，我们进一步发展了蒙特卡洛家系双亲X染色体不对称检验（XMCPPAT），通过对观察到的基因型进行蒙特卡洛估计来推断缺失基因型，以检验亲本起源效应。已经进行了广泛的模拟研究，以调查第一类错误率和拟议测试的威力。仿真结果表明，在没有父源效应的零假设下，所提出的方法可以很好地控制尺寸。此外，XMCPPAT大大优于现有的测试，并且具有比XPPAT高得多的能力，XPPAT只使用来自系谱的完整核心家庭（父母双方）。我们也应用所提出的方法来分析类风湿性关节炎的数据，以供其实际使用。结论所建立的XPPAT和XMCPPAT检验统计量对一般家系定性性状的X染色体亲本效应检测有效，值得推广。
BackgroundGenomic imprinting is one of the well-known epigenetic factors causing the association between traits and genes, and has generally been examined by detecting parent-of-origin effects of alleles. A lot of methods have been proposed to test for parent-of-origin effects on autosomes based on nuclear families and general pedigrees. Although these parent-of-origin effects tests on autosomes have been available for more than 15 years, there has been no statistical test developed to test for parent-of-origin effects on X chromosome, until the parental-asymmetry test on X chromosome (XPAT) and its extensions were recently proposed. However, these methods on X chromosome are only applicable to nuclear families and thus are not suitable for general pedigrees.ResultsIn this article, we propose the pedigree parental-asymmetry test on X chromosome (XPPAT) statistic to test for parent-of-origin effects in the presence of association, which can accommodate general pedigrees. When there are missing genotypes in some pedigrees, we further develop the Monte Carlo pedigree parental-asymmetry test on X chromosome (XMCPPAT) to test for parent-of-origin effects, by inferring the missing genotypes given the observed genotypes based on a Monte Carlo estimation. An extensive simulation study has been carried out to investigate the type I error rates and the powers of the proposed tests. Our simulation results show that the proposed methods control the size well under the null hypothesis of no parent-of-origin effects. Moreover, XMCPPAT substantially outperforms the existing tests and has a much higher power than XPPAT which only uses complete nuclear families (with both parents) from pedigrees. We also apply the proposed methods to analyze rheumatoid arthritis data for their practical use.ConclusionsThe proposed XPPAT and XMCPPAT test statistics are valid and powerful in detecting parent-of-origin effects on X chromosome for qualitative traits based on general pedigrees and thus are recommended.
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