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

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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.