@article{ca20756f72bd41b0a3210a532fdb46a9,
title = "Dog ownership in infancy is protective for persistent wheeze in 17q21 asthma-risk carriers",
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.",
keywords = "17q, ALSPAC, asthma, birth cohort, cat, dog, Gene-environment interaction, LCA, longitudinal, meta-analysis, ownership, STELAR, UNICORN, wheeze",
author = "{STELAR/UNICORN investigators} and Mauro Tutino and Raquel Granell and Curtin, {John A} and Sadia Haider and Sara Fontanella and Murray, {Clare S} and Graham Roberts and Arshad, {S Hasan} and Stephen Turner and Morris, {Andrew P} and Adnan Custovic and Angela Simpson",
note = "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: {\textcopyright} 2022 The Authors",
year = "2023",
month = feb,
day = "1",
doi = "10.1016/j.jaci.2022.10.012",
language = "English",
volume = "151",
pages = "423--430",
journal = "The Journal of allergy and clinical immunology",
issn = "0091-6749",
publisher = "Mosby, Incorporated",
number = "2",
}