Vonk, JM;
Scholtens, S;
Postma, DS;
Moffatt, MF;
Jarvis, D;
Ramasamy, A;
Wjst, M;
Omenaas, ER;
Bouzigon, E;
Demenais, F;
et al.
Vonk, JM; Scholtens, S; Postma, DS; Moffatt, MF; Jarvis, D; Ramasamy, A; Wjst, M; Omenaas, ER; Bouzigon, E; Demenais, F; Nadif, R; Siroux, V; Polonikov, AV; Solodilova, M; Ivanov, VP; Curjuric, I; Imboden, M; Kumar, A; Probst-Hensch, N; Ogorodova, LM; Puzyrev, VP; Bragina, EY; Freidin, MB; Nolte, IM; Farrall, AM; Cookson, WOCM; Strachan, DP; Koppelman, GH; Boezen, HM
(2017)
Adult onset asthma and interaction between genes and active tobacco smoking: The GABRIEL consortium.
PLoS One, 12 (3).
e0172716.
ISSN 1932-6203
https://doi.org/10.1371/journal.pone.0172716
SGUL Authors: Strachan, David Peter
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Abstract
BACKGROUND: Genome-wide association studies have identified novel genetic associations for asthma, but without taking into account the role of active tobacco smoking. This study aimed to identify novel genes that interact with ever active tobacco smoking in adult onset asthma. METHODS: We performed a genome-wide interaction analysis in six studies participating in the GABRIEL consortium following two meta-analyses approaches based on 1) the overall interaction effect and 2) the genetic effect in subjects with and without smoking exposure. We performed a discovery meta-analysis including 4,057 subjects of European descent and replicated our findings in an independent cohort (LifeLines Cohort Study), including 12,475 subjects. RESULTS: First approach: 50 SNPs were selected based on an overall interaction effect at p<10-4. The most pronounced interaction effect was observed for rs9969775 on chromosome 9 (discovery meta-analysis: ORint = 0.50, p = 7.63*10-5, replication: ORint = 0.65, p = 0.02). Second approach: 35 SNPs were selected based on the overall genetic effect in exposed subjects (p <10-4). The most pronounced genetic effect was observed for rs5011804 on chromosome 12 (discovery meta-analysis ORint = 1.50, p = 1.21*10-4; replication: ORint = 1.40, p = 0.03). CONCLUSIONS: Using two genome-wide interaction approaches, we identified novel polymorphisms in non-annotated intergenic regions on chromosomes 9 and 12, that showed suggestive evidence for interaction with active tobacco smoking in the onset of adult asthma.
Item Type: | Article | ||||||
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Additional Information: | © 2017 Vonk et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | ||||||
Keywords: | General Science & Technology, MD Multidisciplinary | ||||||
SGUL Research Institute / Research Centre: | Academic Structure > Population Health Research Institute (INPH) | ||||||
Journal or Publication Title: | PLoS One | ||||||
ISSN: | 1932-6203 | ||||||
Language: | eng | ||||||
Dates: |
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Publisher License: | Creative Commons: Attribution 4.0 | ||||||
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PubMed ID: | 28253294 | ||||||
Go to PubMed abstract | |||||||
URI: | https://openaccess.sgul.ac.uk/id/eprint/108616 | ||||||
Publisher's version: | https://doi.org/10.1371/journal.pone.0172716 |
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