Imperial College London
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PROFESSOR MIRIAM F. MOFFATT

Faculty of Medicine, National Heart & Lung Institute

Consul for the Faculty of Medicine, Professor
 
 
 
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Contact

 

+44 (0)20 7594 2942m.moffatt

 
 
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Location

 

400Guy Scadding BuildingRoyal Brompton Campus

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Summary

 

Publications

Citation

BibTex format

@article{Sugier:2019:10.1111/cea.13476,
author = {Sugier, P-E and Sarnowski, C and Granell, R and Laprise, C and Ege, MJ and Margaritte-Jeannin, P and Dizier, M-H and Minelli, C and Moffatt, MF and Lathrop, M and Cookson, WOCM and Henderson, AJ and von, Mutius E and Kogevinas, M and Demenais, F and Bouzigon, E},
doi = {10.1111/cea.13476},
journal = {Clinical and Experimental Allergy},
pages = {1342--1351},
title = {Genome-wide interaction study of early-life smoking exposure on time-to-asthma onset in childhood},
url = {http://dx.doi.org/10.1111/cea.13476},
volume = {49},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BACKGROUND: Asthma, a heterogeneous disease with variable age of onset, results from the interplay between genetic and environmental factors. Early-life tobacco smoke (ELTS) exposure is a major asthma risk factor. Only a few genetic loci have been reported to interact with ELTS exposure in asthma. OBJECTIVE: Our aim was to identify new loci interacting with ELTS exposure on time-to-asthma onset (TAO) in childhood. METHODS: We conducted genome-wide interaction analyses of ELTS exposure on time-to-asthma onset in childhood in five European-ancestry studies (totaling 8,273 subjects) using Cox proportional-hazard model. The results of all five genome-wide analyses were meta-analyzed. RESULTS: The 13q21 locus showed genome-wide significant interaction with ELTS exposure (P=4.3x10-8 for rs7334050 within KLHL1 with consistent results across the five studies). Suggestive interactions (P<5x10-6 ) were found at three other loci: 20p12 (rs13037508 within MACROD2; P=4.9x10-7 ), 14q22 (rs7493885 near NIN; P=2.9x10-6 ) and 2p22 (rs232542 near CYP1B1; P=4.1x10-6 ). Functional annotations and the literature showed that the lead SNPs at these four loci influence DNA methylation in the blood and are located nearby CpG sites reported to be associated with exposure to tobacco smoke components, which strongly support our findings. CONCLUSION AND CLINICAL RELEVANCE: We identified novel candidate genes interacting with ELTS exposure on time-to-asthma onset in childhood. These genes have plausible biological relevance related to tobacco smoke exposure. Further epigenetic and functional studies are needed to confirm these findings and to shed light on the underlying mechanisms. This article is protected by copyright. All rights reserved.
AU  - Sugier,P-E
AU  - Sarnowski,C
AU  - Granell,R
AU  - Laprise,C
AU  - Ege,MJ
AU  - Margaritte-Jeannin,P
AU  - Dizier,M-H
AU  - Minelli,C
AU  - Moffatt,MF
AU  - Lathrop,M
AU  - Cookson,WOCM
AU  - Henderson,AJ
AU  - von,Mutius E
AU  - Kogevinas,M
AU  - Demenais,F
AU  - Bouzigon,E
DO  - 10.1111/cea.13476
EP  - 1351
PY  - 2019///
SN  - 0954-7894
SP  - 1342
TI  - Genome-wide interaction study of early-life smoking exposure on time-to-asthma onset in childhood
T2  - Clinical and Experimental Allergy
UR  - http://dx.doi.org/10.1111/cea.13476
UR  - https://www.ncbi.nlm.nih.gov/pubmed/31379025
UR  - https://onlinelibrary.wiley.com/doi/abs/10.1111/cea.13476
UR  - http://hdl.handle.net/10044/1/73244
VL  - 49
ER  -
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