Epigenome-wide Association Study of the Effect of Maternal Age on Offspring DNA Methylation
Monday, March 5, 2018
South Hall A2 (Convention Center)
John W. Holloway, BSc PhD, Cory H. White, Ahmad Alzahrani, Hongmei Zhang, PhD, Susan Ewart, Linda S. Mansfield, VMD, PhD, Hasan Arshad, MD, Wilfried Karmaus, MD, Faisal I Rezwan
RATIONALE: Maternal age at birth has been associated with increased incidence of asthma, food allergy, and diabetes in children and young adults. The biological mechanisms underlying these associations remain elusive. One mechanism may be epigenetics.

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.