Sacco Chiara, Viroli Cinzia, Falchi Mario
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Stat Appl Genet Mol Biol. 2017 Sep 26;16(4):275-289. doi: 10.1515/sagmb-2017-0007.
Genomic imprinting is an epigenetic mechanism that leads to differential contributions of maternal and paternal alleles to offspring gene expression in a parent-of-origin manner. We propose a novel test for detecting the parent-of-origin effects (POEs) in genome wide genotype data from related individuals (twins) when the parental origin cannot be inferred. The proposed method exploits a finite mixture of linear mixed models: the key idea is that in the case of POEs the population can be clustered in two different groups in which the reference allele is inherited by a different parent. A further advantage of this approach is the possibility to obtain an estimation of parental effect when the parental information is missing. We will also show that the approach is flexible enough to be applicable to the general scenario of independent data. The performance of the proposed test is evaluated through a wide simulation study. The method is finally applied to known imprinted genes of the MuTHER twin study data.
基因组印记是一种表观遗传机制，它导致母本和父本等位基因以亲本来源的方式对后代基因表达产生不同的贡献。我们提出了一种新颖的检验方法，用于在无法推断亲本来源时，检测来自相关个体（双胞胎）的全基因组基因型数据中的亲本来源效应（POE）。所提出的方法利用了线性混合模型的有限混合：关键思想是，在存在POE的情况下，总体可以聚类为两个不同的组，其中参考等位基因由不同的亲本遗传。这种方法的另一个优点是，当亲本信息缺失时，有可能获得亲本效应的估计值。我们还将表明，该方法足够灵活，适用于独立数据的一般情况。通过广泛的模拟研究评估了所提出检验的性能。该方法最终应用于MuTHER双胞胎研究数据中的已知印记基因。
