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Michel, S.* ; Liang, L.M.* ; Depner, M.* ; Klopp, N. ; Ruether, A.* ; Kumar, A.* ; Schedel, M.* ; Vogelberg, C.* ; von Mutius, E.* ; von Berg, A.* ; Bufe, A.* ; Rietschel, E.* ; Heinzmann, A.* ; Laub, O.* ; Simma, B.* ; Frischer, T.* ; Genuneit, J.* ; Gut, I.G.* ; Schreiber, S.* ; Lathrop, M* ; Illig, T. ; Kabesch, M.*

Unifying candidate gene and GWAS approaches in asthma.

PLoS ONE 5:e13894 (2010)
Publ. Version/Full Text Volltext DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
The first genome wide association study (GWAS) for childhood asthma identified a novel major susceptibility locus on chromosome 17q21 harboring the ORMDL3 gene, but the role of previous asthma candidate genes was not specifically analyzed in this GWAS. We systematically identified 89 SNPs in 14 candidate genes previously associated with asthma in >3 independent study populations. We re-genotyped 39 SNPs in these genes not covered by GWAS performed in 703 asthmatics and 658 reference children. Genotyping data were compared to imputation data derived from Illumina HumanHap300 chip genotyping. Results were combined to analyze 566 SNPs covering all 14 candidate gene loci. Genotyped polymorphisms in ADAM33, GSTP1 and VDR showed effects with p-values <0.0035 (corrected for multiple testing). Combining genotyping and imputation, polymorphisms in DPP10, EDN1, IL12B, IL13, IL4, IL4R and TNF showed associations at a significance level between p = 0.05 and p = 0.0035. These data indicate that (a) GWAS coverage is insufficient for many asthma candidate genes, (b) imputation based on these data is reliable but incomplete, and (c) SNPs in three previously identified asthma candidate genes replicate in our GWAS population with significance after correction for multiple testing in 14 genes.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords NECROSIS-FACTOR-ALPHA; ETHNICALLY DIVERSE POPULATIONS; GENOME-WIDE ASSOCIATION; CHILDHOOD ASTHMA; BRONCHIAL HYPERRESPONSIVENESS; RECEPTOR POLYMORPHISMS; ADAM33 POLYMORPHISMS; ATOPIC ASTHMA; ADULT ASTHMA; BIRTH COHORT
ISSN (print) / ISBN 1932-6203
Journal PLoS ONE
Quellenangaben Volume: 5, Issue: 11, Pages: , Article Number: e13894 Supplement: ,
Publisher Public Library of Science (PLoS)
Publishing Place Lawrence, Kan.
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology (EPI)