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Methylation risk scores for childhood aeroallergen sensitization: Results from the LISA birth cohort
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  • Anna Kilanowski,
  • Junyu Chen,
  • Todd Everson,
  • Elisabeth Thiering,
  • Rory Wilson,
  • Nicole Gladish,
  • Melanie Waldenberger,
  • Hongmei Zhang,
  • Juan C. Celedon,
  • Esteban Burchard,
  • Anette Peters,
  • Marie Standl,
  • Anke Hüls
Anna Kilanowski
Emory University Department of Epidemiology

Corresponding Author:anna.kilanowski@helmholtz-muenchen.de

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Junyu Chen
Emory University Department of Epidemiology
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Todd Everson
Emory University Department of Epidemiology
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Elisabeth Thiering
Helmholtz Zentrum Munchen Institut fur Diabetes und Adipositas
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Rory Wilson
Helmholtz Zentrum Munchen Deutsches Forschungszentrum fur Umwelt und Gesundheit Zentralbibliothek
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Nicole Gladish
The University of British Columbia Centre for Molecular Medicine and Therapeutics
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Melanie Waldenberger
Helmholtz Zentrum Munchen Institut fur Diabetes und Adipositas
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Hongmei Zhang
The University of Memphis School of Public Health
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Juan C. Celedon
Children's Hospital of Pittsburgh of UPMC
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Esteban Burchard
UCSF Department of Bioengineering and Therapeutic Sciences
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Anette Peters
Helmholtz Zentrum Munchen Institut fur Diabetes und Adipositas
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Marie Standl
Helmholtz Zentrum Munchen Institut fur Diabetes und Adipositas
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Anke Hüls
Emory University Department of Epidemiology
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Abstract

Background It has been hypothesized that epigenomic modifications such as genomic methylation changes are an intermediate step linking environmental exposures with allergic disease development. Associations between individual DNA methylation CpG sites and allergic diseases have been reported, but they have not been assessed regarding their joint predictive capability. Methods Data were obtained from 240 children of the German LISA cohort. Blood-based DNA methylation was measured at six and ten years. Aeroallergen sensitization, at least RAST class 1, was measured in blood at six, ten and 15 years. We calculated six methylation risk scores (MRS) for allergy-related phenotypes based on available publications and assessed their performance both cross-sectionally and prospectively. Dose-response associations between aeroallergen sensitization and MRS, their correlation and mapping of common hits were evaluated. Results All six atopy-related MRS were highly correlated (r>0.86) and seven CpGs were included in more than one MRS. Cross-sectionally, we observed an 80% increased risk for aeroallergen sensitization at six years with an increased risk score by one standard deviation (best MRS: relative risk = 1.81, 95% confidence interval = [1.43; 2.27]). Significant associations were also seen at ten years and in prospective models, though the effect of the latter was attenuated when only including participants not sensitized at baseline. A clear dose-response relationship with RAST classes of aeroallergen sensitization could be established cross-sectionally, but not prospectively. Conclusion We found good classification and prediction capabilities of calculated allergy-related MRS, particularly cross-sectionally for the allergy prevalence, underlining the relevance of altered gene-regulation in allergic diseases.
02 Nov 2021Submitted to Allergy
03 Nov 2021Submission Checks Completed
03 Nov 2021Assigned to Editor
06 Nov 2021Reviewer(s) Assigned
19 Nov 2021Review(s) Completed, Editorial Evaluation Pending
22 Nov 2021Editorial Decision: Revise Minor
11 Feb 20221st Revision Received
16 Feb 2022Submission Checks Completed
16 Feb 2022Assigned to Editor
23 Feb 2022Reviewer(s) Assigned
07 Mar 2022Review(s) Completed, Editorial Evaluation Pending
18 Mar 20222nd Revision Received
18 Mar 2022Submission Checks Completed
18 Mar 2022Assigned to Editor
21 Mar 2022Review(s) Completed, Editorial Evaluation Pending
22 Mar 2022Editorial Decision: Accept
Sep 2022Published in Allergy volume 77 issue 9 on pages 2803-2817. 10.1111/all.15315