Intergenerational association of DNA methylation between parents and offspring

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 the parent's DNAm in whole blood. Mothers' DNAm was analyzed at birth (Guthrie card), age 18, early and late pregnancy respectively, and fathers' DNAm was measured during the mother's pregnancy. Linear regressions were applied to assess the intergenerational correlation of parental DNAm with that of offspring. Among various pairs of mother-newborn and father-newborn DNAm, the pairs where the mothers' DNAm was measured at age 18 years exhibited the highest number of CpGs with significant intergenerational correlation in DNAm, with 1829 CpGs (0.54%) of the 338,526 CpGs studied (FDR < 0.05). Amongst these 1829 CpGs, 986 (54%) are known quantitative trait loci (QTL) for CpG methylation (methQTL). When the 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%) was found when investigating DNAm in offspring cord blood and father pairs. The low proportions of intergenerationally correlated CpGs suggest that epigenetic inheritance is limited.

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