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Kilanowski, A. ; Chen, J.* ; Everson, T.* ; Thiering, E. ; Wilson, R. ; Gladish, N.* ; Waldenberger, M. ; Zhang, H.* ; Celedón, J.C.* ; Burchard, E.G.* ; Peters, A. ; Standl, M. ; Hüls, A.*

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

Allergy 77, 2803–2817 (2022)

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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 six (N=234) and ten years (N=227) using the Illumina EPIC chip. Presence of aeroallergen sensitization, was measured in blood at six, ten 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>0.86) and seven CpGs were included in more than one MRS. Cross-sectionally, we observed an 81% increased risk for aeroallergen sensitization at six 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 ten 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.

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