Interaction between the DNAH9 gene and early smoke exposure in bronchial hyper-responsiveness
Interaction between the DNAH9 gene and early smoke exposure in bronchial hyper-responsiveness
A previous genome-wide linkage scan of bronchial hyper-responsiveness (BHR) in EGEA families, performed in presence of G x ETS (early life environmental tobacco smoke) exposure interaction, showed the strongest interaction in 17p11 region where linkage was detected only among unexposed siblings. Our goal was to conduct fine-scale mapping of 17p11 to identify single nucleotide polymorphisms (SNPs) interacting with ETS that influence BHR.
Analyses were performed in 388 French EGEA asthmatic families, using a two-step strategy: 1) selection of SNPs displaying FBAT (family-based association test) association signals (P?0.01) with BHR in unexposed siblings; 2) FBAT homogeneity test between exposed and unexposed siblings plus a robust log-linear interaction test. A single SNP reached the threshold (P? 3.10-3) for significant interaction with ETS using both interaction tests, after accounting for multiple testing. Results were replicated in 253 French-Canadian families but were not in 341 UK families, probably due in part to differences in phenotypic features between datasets.
The SNP showing significant interaction with ETS belongs to DNAH9, a promising candidate gene involved in respiratory cilia mobility and associated with Primary Ciliary Dyskinesia, a disease associated with abnormalities of pulmonary function.
BHR, positional cloning, FBAT, ETS, GxE interaction
1072-1081
Dizier, M.H.
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Nadif, R.
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Margaritte-Jeannin, P.
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Barton, S.J.
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Sarnowski, C.
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Gagne-Ouellet, V.
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Brossard, M.
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Lavielle, N.
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Just, J.
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Lathop, M.
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Holloway, J.W.
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Laprise, C.
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Bouzigon, E.
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Demanais, F.
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April 2016
Dizier, M.H.
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Nadif, R.
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Margaritte-Jeannin, P.
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Barton, S.J.
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Sarnowski, C.
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Gagne-Ouellet, V.
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Brossard, M.
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Lavielle, N.
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Just, J.
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Lathop, M.
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Holloway, J.W.
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Laprise, C.
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Bouzigon, E.
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Demanais, F.
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Dizier, M.H., Nadif, R., Margaritte-Jeannin, P., Barton, S.J., Sarnowski, C., Gagne-Ouellet, V., Brossard, M., Lavielle, N., Just, J., Lathop, M., Holloway, J.W., Laprise, C., Bouzigon, E. and Demanais, F.
(2016)
Interaction between the DNAH9 gene and early smoke exposure in bronchial hyper-responsiveness.
European Respiratory Journal, 47 (4), .
(doi:10.1183/13993003.00849-2015).
Abstract
A previous genome-wide linkage scan of bronchial hyper-responsiveness (BHR) in EGEA families, performed in presence of G x ETS (early life environmental tobacco smoke) exposure interaction, showed the strongest interaction in 17p11 region where linkage was detected only among unexposed siblings. Our goal was to conduct fine-scale mapping of 17p11 to identify single nucleotide polymorphisms (SNPs) interacting with ETS that influence BHR.
Analyses were performed in 388 French EGEA asthmatic families, using a two-step strategy: 1) selection of SNPs displaying FBAT (family-based association test) association signals (P?0.01) with BHR in unexposed siblings; 2) FBAT homogeneity test between exposed and unexposed siblings plus a robust log-linear interaction test. A single SNP reached the threshold (P? 3.10-3) for significant interaction with ETS using both interaction tests, after accounting for multiple testing. Results were replicated in 253 French-Canadian families but were not in 341 UK families, probably due in part to differences in phenotypic features between datasets.
The SNP showing significant interaction with ETS belongs to DNAH9, a promising candidate gene involved in respiratory cilia mobility and associated with Primary Ciliary Dyskinesia, a disease associated with abnormalities of pulmonary function.
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Accepted/In Press date: 18 November 2015
e-pub ahead of print date: 21 January 2016
Published date: April 2016
Keywords:
BHR, positional cloning, FBAT, ETS, GxE interaction
Organisations:
Faculty of Medicine
Identifiers
Local EPrints ID: 385537
URI: http://eprints.soton.ac.uk/id/eprint/385537
ISSN: 0903-1936
PURE UUID: e855bf1e-b075-49c7-8d8a-7414a9483342
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Date deposited: 19 Jan 2016 15:03
Last modified: 15 Mar 2024 05:23
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Contributors
Author:
M.H. Dizier
Author:
R. Nadif
Author:
P. Margaritte-Jeannin
Author:
C. Sarnowski
Author:
V. Gagne-Ouellet
Author:
M. Brossard
Author:
N. Lavielle
Author:
J. Just
Author:
M. Lathop
Author:
C. Laprise
Author:
E. Bouzigon
Author:
F. Demanais
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