Michel, Sven, Liang, Liming, Depner, Martin, Klopp, Norman, Ruether, Andreas, Kumar, Ashish ORCID: 0000-0002-7075-5930, Schedel, Michaela ORCID: 0000-0001-8465-2986, Vogelberg, Christian, von Mutius, Erika ORCID: 0000-0002-8893-4515, von Berg, Andrea, Bufe, Albrecht ORCID: 0000-0001-7335-9362, Rietschel, Ernst, Heinzmann, Andrea, Laub, Otto, Simma, Burkhard, Frischer, Thomas, Genuneit, Jon, Gut, Ivo G., Schreiber, Stefan, Lathrop, Mark, Illig, Thomas and Kabesch, Michael (2010). Unifying Candidate Gene and GWAS Approaches in Asthma. PLoS One, 5 (11). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

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Abstract

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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Michel, SvenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Liang, LimingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Depner, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klopp, NormanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ruether, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kumar, AshishUNSPECIFIEDorcid.org/0000-0002-7075-5930UNSPECIFIED
Schedel, MichaelaUNSPECIFIEDorcid.org/0000-0001-8465-2986UNSPECIFIED
Vogelberg, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
von Mutius, ErikaUNSPECIFIEDorcid.org/0000-0002-8893-4515UNSPECIFIED
von Berg, AndreaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bufe, AlbrechtUNSPECIFIEDorcid.org/0000-0001-7335-9362UNSPECIFIED
Rietschel, ErnstUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heinzmann, AndreaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Laub, OttoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Simma, BurkhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Frischer, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Genuneit, JonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gut, Ivo G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schreiber, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lathrop, MarkUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Illig, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kabesch, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-492527
DOI: 10.1371/journal.pone.0013894
Journal or Publication Title: PLoS One
Volume: 5
Number: 11
Date: 2010
Publisher: PUBLIC LIBRARY SCIENCE
Place of Publication: SAN FRANCISCO
ISSN: 1932-6203
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
NECROSIS-FACTOR-ALPHA; ETHNICALLY DIVERSE POPULATIONS; GENOME-WIDE ASSOCIATION; CHILDHOOD ASTHMA; BRONCHIAL HYPERRESPONSIVENESS; RECEPTOR POLYMORPHISMS; ADAM33 POLYMORPHISMS; ATOPIC ASTHMA; ADULT ASTHMA; BIRTH COHORTMultiple languages
Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/49252

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