METHODS: In peripheral blood samples from the Isle of Wight (IoW) Birth Cohort (10 (N=138) and 18 (N=367) years) and cord-blood samples from 200 subjects from the IoW 3rd Generation Cohort, methylation was assessed using Illumina HumanMethylation450 and EPIC Beadchips and analyzed with linear models. Model 1 treated maternal age at birth as the continuous independent variable and offspring methylation as the dependant variable. Model 2 used maternal age before and after 21 as the nominal variable. Models were adjusted for gender, maternal smoking, parity, maternal socio-economic status, and offspring smoking for 18-year data.
RESULTS: Model 1: 8, 137, and 10 cytosine-phosphate-guanine sites (CpGs) in cord blood, 10, and 18 years, respectively, were statistically significant (FDR = 0.05); Model 2: 1, 67, and 12 CpGs for cord blood, 10, and 18, respectively, were associated with maternal age. In each model, the genes corresponding to the top 100 CpGs ranked by p-value were examined with pathway analysis using Toppgene. In cord blood, enrichment of genes relating to the WnT signalling pathway was identified.
CONCLUSIONS: Methylation at birth of the WnT signalling pathway, which regulates lung development and is associated with airway inflammation and remodelling in asthma, is associated with maternal age. This represents a possible mechanistic link between maternal age and risk of allergic disease.