TY - JOUR AU1 - Sven, Michel AU2 - Liming, Liang AU3 - Martin, Depner AU4 - Norman, Klopp AU5 - Andreas, Ruether AU6 - Ashish, Kumar AU7 - Michaela, Schedel AU8 - Christian, Vogelberg AU9 - Erika, von Mutius AU1 - Andrea, von Berg AU1 - Albrecht, Bufe AU1 - Ernst, Rietschel AU1 - Andrea, Heinzmann AU1 - Otto, Laub AU1 - Burkhard, Simma AU1 - Thomas, Frischer AU1 - Jon, Genuneit AU1 - Ivo G., Gut AU1 - Stefan, Schreiber AU2 - Mark, Lathrop AU2 - Thomas, Illig AU2 - Michael, Kabesch AB - 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. TI - Unifying Candidate Gene and GWAS Approaches in Asthma JF - PLoS ONE DO - 10.1371/journal.pone.0013894 DA - 2010-11-12 UR - https://www.deepdyve.com/lp/public-library-of-science-plos-journal/unifying-candidate-gene-and-gwas-approaches-in-asthma-NlSPsn0AdP VL - 5 IS - 11 DP - DeepDyve ER -