DNA methylation is not associated with sensitization to or dietary introduction of highly allergenic foods in a subset of the CHILD cohort at age 1 year

Kurt P Kolsun; Samantha Lee; Julia L MacIsaac; Padmaja Subbarao; Theo J Moraes; Piushkumar J Mandhane; Stuart E Turvey; Michael S Kobor; Meaghan J Jones; Elinor Simons

doi:10.1016/j.jacig.2023.100130

DNA methylation is not associated with sensitization to or dietary introduction of highly allergenic foods in a subset of the CHILD cohort at age 1 year

J Allergy Clin Immunol Glob. 2023 Jun 26;2(4):100130. doi: 10.1016/j.jacig.2023.100130. eCollection 2023 Nov.

Authors

Affiliations

¹ Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg.
² Department of Medical Genetics, University of British Columbia, Vancouver.
³ Division of Respiratory Medicine, Department of Pediatrics, Hospital for Sick Children and University of Toronto.
⁴ Division of Pediatric Respirology, Pulmonary, and Asthma, Department of Pediatrics, University of Alberta, Edmonton.
⁵ Division of Allergy and Immunology, Department of Pediatrics, British Columbia Children's Hospital, Vancouver.
⁶ Children's Hospital Research Institute of Manitoba, Winnipeg.
⁷ Section of Allergy and Immunology, Department of Pediatrics and Child Health, University of Manitoba, Winnipeg.

Abstract

Background: In the first year of life, DNA methylation (DNAm) patterns are established and are particularly susceptible to exposure-induced changes. Some of these changes may leave lasting effects by persistently altering gene expression or cell type composition or function, contributing to disease.

Objectives: In this discovery study, we investigated DNAm associations with sensitization to peanut, egg, or cow's milk and hypothesized that genes demonstrating DNAm differences in immune cells may play a role in the development of food sensitization.

Methods: Infant sensitization (a skin prick test wheal size that is at least 2 mm greater than the negative control) was measured to peanut, egg, and cow's milk at age 1 year, and ages of food introduction were reported prospectively. PBMC DNAm was measured in blood samples at 1 year in 144 infants, oversampled for atopy or wheeze. Statistical analysis of Illumina 450k array DNAm data was conducted in R with adjustment for clinical and genetic covariables and a minimum effect size of 1%, false discovery rate of 5%, and medium-confidence false discovery rate threshold of 20%.

Results: There were no DNAm differences between infants with and without peanut, egg, or cow's milk sensitization. Borderline significant sites with high effect sizes were enriched for methylation quantitative trait loci, hinting at genetic factors influencing DNAm at these sites. DNAm patterns did not differ by peanut or egg introduction before or after 12 months.

Conclusion: This small pilot study did not show differences in methylation by food sensitization or introduction, but it did demonstrate DNAm patterns linked to genetic variants.

Keywords: CHILD Cohort Study; DNA methylation; allergenic food; egg; epigenetic; food allergy; food introduction; food sensitization; peanut.