Epigenome-Wide Assessment on DNA Methylation Change with Asthma Transition in Adolescence

Adolescence is a period of significant gender-dependent changes. Due to increased new onset and reduced remission in girls, a gender reversal occurs with asthma prevalence in females surpassing that of males. The causes of negative, persistent, and positive transition of asthma are unclear. We explored whether changes in DNA methylation (DNAm) between ages 10 and 18 are associated with asthma transition. We used data from a population-based birth cohort (N=1456) established on the Isle of Wight (IoW), UK followed up at ages 1, 2, 4, 10 and 18 years. We collected information on asthma and allergy. Diagnosis of asthma was based on ISAAC questionnaire clinical assessment. DNAm was measured in peripheral blood at 10 (n=329) and 18 (n=476) years of age using Illumina Infinium Human Methylation 450 and EPIC Beadchips. Logistic regression was implemented with asthma transition status as the response variable, controlled for potential confounders including gender, family history of asthma, gestational maternal smoking, allergy, current smoking, birthweight, farm living, paracetamol use, social class, pet exposure, breast feeding, height and BMI changes. Multiple testing was adjusted by controlling false discovery rate of 0.05. DNAm at 7 Cytosine-Phosphate-Guanine (CPG) sites was associated with negative transition, 17 with positive transition, and 3 with persistent asthma. These 27 CpGs correspond to 19 genes and 8 inter-genetic regions, including ACADVL and SLC12A2 which have previously been implicated in asthma and other airway disease. The result implies that the 27 CpGs are potential epigenetic markers for asthma transition.