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Castro-Giner, F., Bustamante, M., Gonzalez, J. R., Kogevinas, M., Jarvis, D., Heinrich, J., Anto, J. M., Wjst, M., Estivill, X., De Cid, R

A pooling-based genome-wide analysis identifies new potential candidate genes for atopy in the European Community Respiratory Health Survey (ECRHS)

BMC.Med.Genet., 2009, 10, 1, , 28, IF: 2.840, PMID: 19961619

ABSTRACT: BACKGROUND: Asthma and atopy are complex phenotypes with shared genetic component. In this study we attempt to identify genes related to these traits performing a two-stage DNA pooling genome-wide analysis in order to reduce costs. First, we assessed all markers in a subset of subjects using DNA pooling, and in a second stage we evaluated the most promising markers at an individual level. METHODS: For the genome-wide analysis, we constructed DNA pools from 75 subjects with atopy and asthma, 75 subjects with atopy and without asthma and 75 control subjects without atopy or asthma. In a second stage, the most promising regions surrounding significant markers after correction for false discovery rate were replicated with individual genotyping of samples included in the pools and an additional set of 429 atopic subjects and 222 controls from the same study centres. RESULTS: Homo sapiens protein kinase-like protein SgK493 (SGK493) was found to be associated with atopy. To lesser extent mitogen-activated protein kinase 5 (MAP3K5), collagen type XVIII alpha 1 (COL18A1) and collagen type XXIX alpha 1 (COL29A1) were also found to be associated with atopy. Functional evidences points out a role for MAP3K5, COL18A1 and COL29A1 but the function of SGK493 is unknown. CONCLUSIONS: In this analysis we have identified new candidate regions related to atopy and suggest SGK493 as an atopy locus, although these results need further replication

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