Dog ownership in infancy is protective for persistent wheeze in 17q21 asthma-risk carriers
Dog ownership in infancy is protective for persistent wheeze in 17q21 asthma-risk carriers
Background: Asthma-associated single nucleotide polymorphisms from large genome-wide association studies only explain a fraction of genetic heritability. Likely causes of the missing heritability include broad phenotype definitions and gene-environment interactions (GxE). The mechanisms underlying GxE in asthma are poorly understood. Previous GxE studies on pet ownership showed discordant results. Objectives: We sought to study the GxE between the 17q12-21 locus and pet ownership in infancy in relation to wheeze. Methods: Wheezing classes derived from 5 UK-based birth cohorts (latent class analysis) were used to study GxE between the 17q12-21 asthma-risk variant rs2305480 and dog and cat ownership in infancy, using multinomial logistic regression. A total of 9149 children had both pet ownership and genotype data available. Summary statistics from individual analyses were meta-analyzed. Results: rs2305480 G allele was associated with increased risk of persistent wheeze (additive model odds ratio, 1.37; 95% CI, 1.25-1.51). There was no evidence of an association between dog or cat ownership and wheeze. We found significant evidence of a GxE interaction between rs2305480 and dog ownership (P = 8.3 × 10
−4) on persistent wheeze; among dog owners, the G allele was no longer associated with an increased risk of persistent wheeze (additive model odds ratio, 0.95; 95% CI, 0.73-1.24). For those without pets, G allele was associated with increased risk of persistent wheeze (odds ratio, 1.61; 95% CI, 1.40-1.86). Among cat owners, no such dampening of the genetic effect was observed. Conclusions: Among dog owners, rs2305480 G was no longer associated with an increased risk of persistent wheeze (or asthma). Early-life environmental exposures may therefore attenuate likelihood of asthma in those carrying 17q12-21 risk alleles.
17q, ALSPAC, Gene-environment interaction, LCA, STELAR, UNICORN, asthma, birth cohort, cat, dog, longitudinal, meta-analysis, ownership, wheeze
Tutino, M.
db58c966-545c-40f7-aa8d-05c34cfb9bd9
Granell, R.
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Curtin, J.A.
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Haider, S.
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Fontanella, S.
ffb87354-534d-43da-829d-cfba6d0db6ca
Murray, C.S.
aafef9e5-c983-43fa-b12e-c73ea8e4f3ae
Roberts, G.
ea00db4e-84e7-4b39-8273-9b71dbd7e2f3
Arshad, S.H.
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Turner, S.
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Morris, A.P.
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Custovic, A.
624645ad-f4d2-4b1f-a9b6-a8bd763a8d84
Simpson, A.
5d26fc74-8447-4047-aa4f-1ca147a11392
STELAR/UNICORN investigators
Tutino, M.
db58c966-545c-40f7-aa8d-05c34cfb9bd9
Granell, R.
7cffe794-576c-4a1a-bed6-ec2c3b202e75
Curtin, J.A.
b1f4f316-b8a3-438f-aeab-4c411ab41da2
Haider, S.
8f4f1f66-534d-4c15-a297-22994e61beae
Fontanella, S.
ffb87354-534d-43da-829d-cfba6d0db6ca
Murray, C.S.
aafef9e5-c983-43fa-b12e-c73ea8e4f3ae
Roberts, G.
ea00db4e-84e7-4b39-8273-9b71dbd7e2f3
Arshad, S.H.
917e246d-2e60-472f-8d30-94b01ef28958
Turner, S.
f401be82-90e2-4da9-8a3d-48f5a2cb85d0
Morris, A.P.
e0469a33-12f5-4f61-8270-d51272fd31df
Custovic, A.
624645ad-f4d2-4b1f-a9b6-a8bd763a8d84
Simpson, A.
5d26fc74-8447-4047-aa4f-1ca147a11392
Tutino, M., Granell, R. and Curtin, J.A.
,
STELAR/UNICORN investigators
(2022)
Dog ownership in infancy is protective for persistent wheeze in 17q21 asthma-risk carriers.
The Journal of Allergy and Clinical Immunology.
(doi:10.1016/j.jaci.2022.10.012).
Abstract
Background: Asthma-associated single nucleotide polymorphisms from large genome-wide association studies only explain a fraction of genetic heritability. Likely causes of the missing heritability include broad phenotype definitions and gene-environment interactions (GxE). The mechanisms underlying GxE in asthma are poorly understood. Previous GxE studies on pet ownership showed discordant results. Objectives: We sought to study the GxE between the 17q12-21 locus and pet ownership in infancy in relation to wheeze. Methods: Wheezing classes derived from 5 UK-based birth cohorts (latent class analysis) were used to study GxE between the 17q12-21 asthma-risk variant rs2305480 and dog and cat ownership in infancy, using multinomial logistic regression. A total of 9149 children had both pet ownership and genotype data available. Summary statistics from individual analyses were meta-analyzed. Results: rs2305480 G allele was associated with increased risk of persistent wheeze (additive model odds ratio, 1.37; 95% CI, 1.25-1.51). There was no evidence of an association between dog or cat ownership and wheeze. We found significant evidence of a GxE interaction between rs2305480 and dog ownership (P = 8.3 × 10
−4) on persistent wheeze; among dog owners, the G allele was no longer associated with an increased risk of persistent wheeze (additive model odds ratio, 0.95; 95% CI, 0.73-1.24). For those without pets, G allele was associated with increased risk of persistent wheeze (odds ratio, 1.61; 95% CI, 1.40-1.86). Among cat owners, no such dampening of the genetic effect was observed. Conclusions: Among dog owners, rs2305480 G was no longer associated with an increased risk of persistent wheeze (or asthma). Early-life environmental exposures may therefore attenuate likelihood of asthma in those carrying 17q12-21 risk alleles.
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Accepted/In Press date: 2022
e-pub ahead of print date: 20 October 2022
Additional Information:
Funding Information:
Manchester Asthma and Allergy Study was supported by Asthma UK (grant nos. 301 [1995-1998], 362 [1998-2001)], 01/012 [2001-2004], and 04/014 [2004-2007]), BMA James Trust (2005), and The JP Moulton Charitable Foundation (2004-current), The North West Lung Centre Charity (1997-current), and the Medical Research Council (MRC) (grant nos. G0601361 [2007-2012], MR/K002449/1 [2013-2014], and MR/L012693/1 [2014-2018]). The 10-year follow-up of the Isle of Wight Whole Population Birth Cohort was funded by the National Asthma Campaign, UK (grant no. 364). Avon Longitudinal Study of Parents and Children (ALSPAC) was supported by the MRC Programme (grant no. MR/S025340/1) and Wellcome Trust Strategic Award (108,818/15/Z). The UK MRC and Wellcome (grant reference 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. This publication is the work of the authors and Raquel Granell will serve as guarantors for the contents of this article. A.S., C.M., and M.T. are supported by the National Institute for Health Research Manchester Biomedical Research Centre . The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research, or the Department of Health.
Funding Information:
We thank the study participants and their parents for their continued support and enthusiasm. We greatly appreciate the commitment they have given to the project. We acknowledge the hard work and dedication of the study teams (postdoctoral scientists, physiologists, research fellows, nurses, technicians, and clerical staff). We acknowledge the help of all the staff at the David Hide Asthma and Allergy Research Centre in undertaking the assessments of the Isle of Wight Birth Cohort. Recruitment and initial assessment for the first 4 years of age for the Isle of Wight Whole Population Birth Cohort were supported by the Isle of Wight Health Authority.
Publisher Copyright:
© 2022 The Authors
Keywords:
17q, ALSPAC, Gene-environment interaction, LCA, STELAR, UNICORN, asthma, birth cohort, cat, dog, longitudinal, meta-analysis, ownership, wheeze
Identifiers
Local EPrints ID: 472046
URI: http://eprints.soton.ac.uk/id/eprint/472046
ISSN: 0091-6749
PURE UUID: 7987af26-f276-4218-8ff3-5a0f241559c1
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Date deposited: 24 Nov 2022 17:39
Last modified: 17 Mar 2024 03:02
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Contributors
Author:
M. Tutino
Author:
R. Granell
Author:
J.A. Curtin
Author:
S. Haider
Author:
S. Fontanella
Author:
C.S. Murray
Author:
S. Turner
Author:
A.P. Morris
Author:
A. Custovic
Author:
A. Simpson
Corporate Author: STELAR/UNICORN investigators
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