Nieuwenhuis, M. A. and Siedlinski, M. and van den Berge, M. and Granell, R. and Li, X. and Niens, M. and van der Vlies, P. and Altmueller, J. and Nuernberg, P. and Kerkhof, M. and van Schayck, O. C. and Riemersma, R. A. and van der Molen, T. and de Monchy, J. G. and Bosse, Y. and Sandford, A. and Bruijnzeel-Koomen, C. A. and Gerth van Wijk, R. and ten Hacken, N. H. and Timens, W. and Boezen, H. M. and Henderson, J. and Kabesch, M. and Vonk, J. M. and Postma, D. S. and Koppelman, G. H. (2016) Combining genomewide association study and lung eQTL analysis provides evidence for novel genes associated with asthma. ALLERGY, 71 (12). pp. 1712-1720. ISSN 0105-4538, 1398-9995
Full text not available from this repository. (Request a copy)Abstract
BackgroundGenomewide association studies (GWASs) of asthma have identified single-nucleotide polymorphisms (SNPs) that modestly increase the risk for asthma. This could be due to phenotypic heterogeneity of asthma. Bronchial hyperresponsiveness (BHR) is a phenotypic hallmark of asthma. We aim to identify susceptibility genes for asthma combined with BHR and analyse the presence of cis-eQTLs among replicated SNPs. Secondly, we compare the genetic association of SNPs previously associated with (doctor's diagnosed) asthma to our GWAS of asthma with BHR. MethodsA GWAS was performed in 920 asthmatics with BHR and 980 controls. Top SNPs of our GWAS were analysed in four replication cohorts, and lung cis-eQTL analysis was performed on replicated SNPs. We investigated association of SNPs previously associated with asthma in our data. ResultsA total of 368 SNPs were followed up for replication. Six SNPs in genes encoding ABI3BP, NAF1, MICA and the 17q21 locus replicated in one or more cohorts, with one locus (17q21) achieving genomewide significance after meta-analysis. Five of 6 replicated SNPs regulated 35 gene transcripts in whole lung. Eight of 20 asthma-associated SNPs from previous GWAS were significantly associated with asthma and BHR. Three SNPs, in IL-33 and GSDMB, showed larger effect sizes in our data compared to published literature. ConclusionsCombining GWAS with subsequent lung eQTL analysis revealed disease-associated SNPs regulating lung mRNA expression levels of potential new asthma genes. Adding BHR to the asthma definition does not lead to an overall larger genetic effect size than analysing (doctor's diagnosed) asthma.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; CANDIDATE GENE; POLYMORPHISMS; CHILDREN; IDENTIFICATION; METAANALYSIS; FLUTICASONE; POPULATION; ALLERGY; asthma; bronchial hyperresponsiveness; gene expression; genetics; genomewide association studies |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Kinder- und Jugendmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 10 Apr 2019 13:23 |
| Last Modified: | 10 Apr 2019 13:23 |
| URI: | https://pred.uni-regensburg.de/id/eprint/3902 |
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