Anna Kilanowski1,2,3,4, Junyu Chen1, Todd Everson1,5, Elisabeth Thiering3,4, Rory Wilson6, Nicole Gladish7,8, Melanie Waldenberger3,6, Hongmei Zhang9, Juan C Celedón10, Esteban G Burchard11, Annette Peters3,12, Marie Standl3,13, Anke Hüls1,5. 1. Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA. 2. Institute for Medical Information Processing, Biometry, and Epidemiology; Pettenkofer School of Public Health, LMU Munich, Munich, Germany. 3. Institute of Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany. 4. Division of Metabolic and Nutritional Medicine, Dr. von Hauner Children's Hospital, University of Munich Medical Center, Munich, Germany. 5. Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA. 6. Research Unit Molecular Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany. 7. Centre for Molecular Medicine and Therapeutics, British Columbia Children's Hospital, Vancouver, BC, Canada. 8. Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada. 9. Division of Epidemiology, Biostatistics, and Environmental Health Sciences, School of Public Health, University of Memphis, Memphis, Tennessee, USA. 10. Division of Pediatric Pulmonary Medicine, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. 11. UCSF Asthma Collaboratory, University of California, San Francisco, California, USA. 12. Chair of Epidemiology, Ludwig-Maximilians University, Munich, Germany. 13. German Center for Lung Research (DZL), Gießen, Germany.
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.
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.
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