Identifizierung und Charakterisierung von Parent-of-origin Effekten beim atopischen Ekzem - Identification and functional analysis of parent-of-origin effects in eczema

湿疹是一种常见的慢性炎症性皮肤病，病因复杂。独立研究表明，患有湿疹的母亲的孩子比患有湿疹的父亲的孩子患湿疹的风险更高（原生父母效应）。原生父母效应可能是由于基因组印记和/或妊娠或哺乳期胎母相互作用（母体效应）。我们建议通过分析一组270个完整的湿疹核心家庭来研究父母的起源效应，其中高密度SNP数据在我们的实验室中可用。有趣的是，在这些家庭中，母亲患湿疹的频率比父亲高得多（分别为32%和18%），这支持了原生父母效应的存在。我们使用亲本似然比检验（PO-LRT检验）对基因型数据进行分析，以检测亲本和母本的影响。重要的是，我们的扫描倾向于识别包含预测或实验验证的印迹基因的基因组区域，支持我们方法的有效性（P < 0.05）。我们建议根据我们的PO-LRT结果选择一组96个显示印迹或母体效应的snp，并在1000个湿疹家族的独立样本中测试它们的复制性。将进行表达和表观遗传学分析，以便为鉴定的候选基因提供印迹的功能证据。这将是第一个在全基因组水平上解决湿疹中父母起源效应的研究，为该疾病病因学的这一有趣方面提供了新的信息。

Eczema is a common chronic inflammatory skin disease with complex etiology. Independent studies have shown that children eczema-affected mothers have a higher risk to develop the disease than children of eczema-affected fathers (parent-of-origin effect). Parent-of-origin effects may be due to genomic imprinting and/or feto-maternal interaction during pregnancy or lactation (maternal effect). We propose to study parent-of-origin effects in eczema by analyzing a set of 270 complete nuclear families with eczema in which high-density SNP data is available in our laboratory. Interestingly, in these families the frequency of eczema is much higher in the mothers than in the fathers (32% versus 18%, respectively), supporting the existence of parent-of-origin effects. We have analyzed the genotype data using the parent-of-origin likelihood ratio test (PO-LRT test) to detect of parent-of-origin and maternal effects. Importantly, our scan tends to identify genomic regions containing predicted or experimentally validated imprinted genes, supporting the validity of our approach (P < 0.05). We propose to select a set of 96 SNPs showing imprinting or maternal effects based on our PO-LRT results and to test them for replication in an independent sample of 1000 eczema families. Expression and epigenetic analyses will be performed in order to provide functional evidence of imprinting for the candidate genes identified. This will be the first study addressing parent-of-origin effects in eczema at a genome-wide level, providing novel information on this interesting aspect of the disease etiology.