Methylation risk scores for childhood aeroallergen sensitization: Results from the LISA birth cohort.

Abstract

BACKGROUND:

Epigenomic (e.g., DNA methylation [DNAm]) changes have been hypothesized as intermediate step linking environmental exposures with allergic disease. Associations between individual DNAm at CpGs and allergic diseases have been reported, but their joint predictive capability is unknown.

METHODS:

Data were obtained from 240 children of the German LISA cohort. DNAm was measured in blood clots at 6 (N = 234) and 10 years (N = 227) using the Illumina EPIC chip. Presence of aeroallergen sensitization was measured in blood at 6, 10, and 15 years. We calculated six methylation risk scores (MRS) for allergy-related phenotypes, like total and specific IgE, asthma, or any allergies, based on available publications and assessed their performances both cross-sectionally (biomarker) and prospectively (predictor of the disease). Dose-response associations between aeroallergen sensitization and MRS were evaluated.

RESULTS:

All six allergy-related MRS were highly correlated (r > .86), and seven CpGs were included in more than one MRS. Cross-sectionally, we observed an 81% increased risk for aeroallergen sensitization at 6 years with an increased MRS by one standard deviation (best-performing MRS, 95% confidence interval = [43%; 227%]). Significant associations were also seen cross-sectionally at 10 years and prospectively, though the effect of the latter was attenuated when restricted to participants not sensitized at baseline. A clear dose-response relationship with levels of aeroallergen sensitization could be established cross-sectionally, but not prospectively.

CONCLUSION:

We found good classification and prediction capabilities of calculated allergy-related MRS cross-sectionally, underlining the relevance of altered gene-regulation in allergic diseases and providing insights into potential DNAm biomarkers of aeroallergen sensitization.

• Authors: Anna Kilanowski, Junyu Chen, Todd Everson, Elisabeth Thiering, Rory Wilson, Nicole Gladish, Melanie Waldenberger, Hongmei Zhang, Juan C Celedón, Esteban G Burchard, Annette Peters, Marie Standl, Anke Hüls
• Journal: Allergy (Allergy) Vol. 77 Issue 9 Pg. 2803-2817 (09 2022) ISSN: 1398-9995 [Electronic] Denmark
• PMID: 35437756 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural)
• Copyright: © 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.

Chemical References

• Allergens
• Biomarkers

Topics

• Allergens
• Biomarkers
• Birth Cohort
• DNA Methylation
• Humans
• Hypersensitivity (diagnosis, epidemiology, etiology)
• Risk Factors