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Genetic susceptibility to asthma increases the vulnerability to indoor air pollution

Anke Hüls, Aneesa Vanker, Diane Gray, Nastassja Koen, Julia L. MacIsaac, David T.S. Lin, Katia E. Ramadori, Peter D. Sly, Dan J. Stein, Michael S. Kobor, Heather J. Zar
European Respiratory Journal 2020; DOI: 10.1183/13993003.01831-2019
Anke Hüls
1Department of Human Genetics, Emory University, Atlanta, Georgia, USA
2Centre for Molecular Medicine and Therapeutics, BC Children's Hospital Research Institute, Vancouver, Canada
3Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada
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  • ORCID record for Anke Hüls
  • For correspondence: anke.huels@emory.edu
Aneesa Vanker
4Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital and SA-MRC Unit on Child and Adolescent Health, University of Cape Town
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Diane Gray
4Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital and SA-MRC Unit on Child and Adolescent Health, University of Cape Town
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Nastassja Koen
5Department of Psychiatry and Mental Health, University of Cape Town, South Africa
6South African Medical Research Council (SAMRC) Unit on Risk and Resilience in Mental Disorders, South Africa
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Julia L. MacIsaac
2Centre for Molecular Medicine and Therapeutics, BC Children's Hospital Research Institute, Vancouver, Canada
3Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada
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David T.S. Lin
2Centre for Molecular Medicine and Therapeutics, BC Children's Hospital Research Institute, Vancouver, Canada
3Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada
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Katia E. Ramadori
2Centre for Molecular Medicine and Therapeutics, BC Children's Hospital Research Institute, Vancouver, Canada
3Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada
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Peter D. Sly
7Children's Health and Environment Program, Child Health Research Centre, The University of Queensland, Brisbane, Queensland, Australia
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Dan J. Stein
5Department of Psychiatry and Mental Health, University of Cape Town, South Africa
6South African Medical Research Council (SAMRC) Unit on Risk and Resilience in Mental Disorders, South Africa
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Michael S. Kobor
2Centre for Molecular Medicine and Therapeutics, BC Children's Hospital Research Institute, Vancouver, Canada
3Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada
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Heather J. Zar
4Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital and SA-MRC Unit on Child and Adolescent Health, University of Cape Town
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Abstract

Introduction Indoor air pollution and maternal smoking during pregnancy are associated with respiratory symptoms in infants, but little is known about the direct association with lung function or interactions with genetic risk factors. We examined associations of indoor particulate matter of diameter ≤10 µm (PM10) exposure and maternal smoking with infant lung function and the role of gene-environment interactions.

Methods Data from the Drakenstein Child Health Study, a South African birth cohort, were analysed (N=270). Lung function was measured at 6 weeks and 1 year of age and lower respiratory tract illness (LRTI) episodes were documented. We measured prenatal and postnatal PM10 exposures using devices placed in homes and prenatal tobacco smoke exposure using maternal urine cotinine levels. Genetic risk scores (GRS) determined from associations with childhood-onset asthma (COA) in the UK Biobank were used to investigate effect modifications.

Results Pre- and postnatal exposure to PM10 as well as maternal smoking during pregnancy were associated with reduced lung function at 6 weeks and 1 year as well as LRTI in the first year. Due to a significant interaction between the GRS and prenatal exposure to PM10, infants carrying more COA-risk alleles were more susceptible to PM10-associated reduced lung function (p-interaction=0.007). This interaction was stronger in infants with black African ancestry (p-interaction=0.001) and non-existent in children with mixed ancestry (p-interaction=0.876).

Conclusions PM10 and maternal smoking exposures were associated with reduced lung function, with a higher susceptibility for infants with an adverse genetic predisposition for asthma that also depended on the infant's ancestry.

Footnotes

This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.

Conflict of interest: Dr. Huels has nothing to disclose.

Conflict of interest: Dr. Vanker reports grants from Bill & Melinda Gates Foundation (OPP1017641, grants from Discovery Foundation, grants from South African Thoracic Society AstraZeneca Respiratory Fellowship, grants from National Research Fund, South Africa, grants from CIDRI Clinical Fellowship, grants from Medical Research Council, South Africa, during the conduct of the study.

Conflict of interest: Dr. Gray has nothing to disclose.

Conflict of interest: Dr. Koen has nothing to disclose.

Conflict of interest: Dr. MacIsaac has nothing to disclose.

Conflict of interest: Dr. Lin has nothing to disclose.

Conflict of interest: Dr. Ramadori has nothing to disclose.

Conflict of interest: Dr. Sly has nothing to disclose.

Conflict of interest: Dr. Stein reports personal fees from Lundbeck, personal fees from Biocodex, personal fees from Sun, outside the submitted work.

Conflict of interest: Dr. Kobor has nothing to disclose.

Conflict of interest: Dr. Zar reports grants from Bill and Melinda Gates Foundation, grants from NIH, grants from Wellcome Trust, grants from SA MRC, grants from National Research Foundation SA, grants from South African Thoracic Society, during the conduct of the study.

This is a PDF-only article. Please click on the PDF link above to read it.

  • Received September 18, 2019.
  • Accepted December 21, 2019.
  • Copyright ©ERS 2020
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Genetic susceptibility to asthma increases the vulnerability to indoor air pollution
Anke Hüls, Aneesa Vanker, Diane Gray, Nastassja Koen, Julia L. MacIsaac, David T.S. Lin, Katia E. Ramadori, Peter D. Sly, Dan J. Stein, Michael S. Kobor, Heather J. Zar
European Respiratory Journal Jan 2020, 1901831; DOI: 10.1183/13993003.01831-2019

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Genetic susceptibility to asthma increases the vulnerability to indoor air pollution
Anke Hüls, Aneesa Vanker, Diane Gray, Nastassja Koen, Julia L. MacIsaac, David T.S. Lin, Katia E. Ramadori, Peter D. Sly, Dan J. Stein, Michael S. Kobor, Heather J. Zar
European Respiratory Journal Jan 2020, 1901831; DOI: 10.1183/13993003.01831-2019
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