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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
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
0903-1936
1072-1081
Dizier, M.H.
7c67e3df-ef18-43d4-b111-eb62db962a08
Nadif, R.
bece6796-ff1a-489a-b9f7-d55b85232a0b
Margaritte-Jeannin, P.
c3235b9b-6156-4d52-9352-044e1f792bcf
Barton, S.J.
4f674382-ca0b-44ad-9670-e71a0b134ef0
Sarnowski, C.
bada389f-6b59-4382-9207-4240183355f5
Gagne-Ouellet, V.
c93b90aa-4518-4397-a15d-90dda967eb0d
Brossard, M.
0e36d99c-5900-4386-960b-d2aa88df7322
Lavielle, N.
2a77a934-ef94-494c-855e-d861be5e4df3
Just, J.
7d59f75d-0c0b-4c6e-8c71-1b7ce1735269
Lathop, M.
4ebba902-7976-4289-b4eb-0574c15a4bee
Holloway, J.W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Laprise, C.
57260109-0c7a-4a2c-af55-bbab912c9115
Bouzigon, E.
86b3bd39-0ad2-4e00-bbe8-508fe45765f0
Demanais, F.
882c668d-099d-4a48-b636-057478966f70
Dizier, M.H.
7c67e3df-ef18-43d4-b111-eb62db962a08
Nadif, R.
bece6796-ff1a-489a-b9f7-d55b85232a0b
Margaritte-Jeannin, P.
c3235b9b-6156-4d52-9352-044e1f792bcf
Barton, S.J.
4f674382-ca0b-44ad-9670-e71a0b134ef0
Sarnowski, C.
bada389f-6b59-4382-9207-4240183355f5
Gagne-Ouellet, V.
c93b90aa-4518-4397-a15d-90dda967eb0d
Brossard, M.
0e36d99c-5900-4386-960b-d2aa88df7322
Lavielle, N.
2a77a934-ef94-494c-855e-d861be5e4df3
Just, J.
7d59f75d-0c0b-4c6e-8c71-1b7ce1735269
Lathop, M.
4ebba902-7976-4289-b4eb-0574c15a4bee
Holloway, J.W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Laprise, C.
57260109-0c7a-4a2c-af55-bbab912c9115
Bouzigon, E.
86b3bd39-0ad2-4e00-bbe8-508fe45765f0
Demanais, F.
882c668d-099d-4a48-b636-057478966f70

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), 1072-1081. (doi:10.1183/13993003.00849-2015).

Record type: Article

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
ORCID for S.J. Barton: ORCID iD orcid.org/0000-0003-4963-4242
ORCID for J.W. Holloway: ORCID iD orcid.org/0000-0001-9998-0464

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Date deposited: 19 Jan 2016 15:03
Last modified: 18 Feb 2021 16:57

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Contributors

Author: M.H. Dizier
Author: R. Nadif
Author: P. Margaritte-Jeannin
Author: S.J. Barton ORCID iD
Author: C. Sarnowski
Author: V. Gagne-Ouellet
Author: M. Brossard
Author: N. Lavielle
Author: J. Just
Author: M. Lathop
Author: J.W. Holloway ORCID iD
Author: C. Laprise
Author: E. Bouzigon
Author: F. Demanais

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