Intergenerational transfer of parental DNA methylation to their newborns?

Abstract Early patterning of DNA methylation (DNAm) may play an important role in later disease development. To better understand intergenerational epigenetic inheritance, we investigated the correlation between DNAm in blood in mother-newborn and in father-newborn pairs in the Isle of Wight (IoW) birth cohort. For parent-newborn pairs (n = 48), offspring DNAm was measured in cord blood and parent’s DNAm in whole blood. Mothers’ DNAm was analyzed at birth (Guthrie card), age 18, early and late pregnancy respectively, and father’s DNAm was measured during mother’s pregnancy. Linear regressions, with cell type compositions included as confounders, were applied to assess the intergenerational correlation of parental DNAm with that of offspring. Of the 338,526 CpGs studied, after controlling a false discovery rate of 0.05, among all the different stages of mother-newborn and father-newborn pairs, mother-newborn pairs with mothers’ DNAm measured at age 18 years showed the largest number of CpGs, 1829 (0.54%) in total, with intergenerational correlation in DNAm. Among the 1829 CpGs, 986 (54%) are known quantitative trait loci (QTL) for CpG methylation (methQTL). When mother’s DNAm was assessed at early pregnancy, the number of CpGs showing intergenerational correlation was the smallest (384 CpGs, 0.11%). The second smallest number of such CpGs (559 CpGs, 0.17%) were found when investigating DNAm in offspring cord blood and father pairs. The low proportions of intergenerationally correlated CpGs suggest that epigenetic inheritance is limited.