Stress, heritability, tissue type and human methylome variation in mother-newborn dyads

Abstract DNA methylation variation has been implicated as a factor that influences inter-individual and inter-tissue phenotypic variation in numerous organisms and under various conditions. Here, using a unique collection of three tissues, derived from 24 mother-newborn dyads from war-torn Democratic Republic of Congo, we estimate how stress, heritability, tissue type and genomic/regulatory context influence genome-wide DNA methylation. We also evaluate if stress-associated variation may mediate an observed phenotype - newborn birthweight. On average, a minimal influence of stress and heritability are observed, while in contrast extensive among tissues and context dependency is evident. However, a notable overlap in heritable and stress-associated variation is observed and that variation is commonly correlated with birthweight variation. Finally, we observe that variation outside of promoter regions, particularly in enhancers, is far more dynamic across tissues and across conditions than in promoters, suggesting that variation outside of promoters may play a larger role in expression variation than variation found within promoter regions.