Longitudinal studies at birth and age 7 reveal strong effects of genetic variation on ancestry-associated DNA methylation patterns in blood cells from ethnically admixed children

The epigenetic architecture in humans is influenced by genetic factors, exposure histories and biological factors such as age, but little is known about their relative contribution or their longitudinal dynamics. Here, we studied DNA methylation levels at over 750,000 CpG sites in mononuclear blood cells collected at birth and age 7 from 196 children of primarily self-reported Black and Hispanic ethnicities to study age- and ancestry-related patterns in DNA methylation. We first identified a large set of age-related CpGs at birth and age 7 and showed that gestational age related CpGs at birth are the same as the age-related CpGs at age 7. We then developed a novel Bayesian inference method for longitudinal data and showed that the vast majority of the ancestry-associated methylation patterns present at birth are also present at age 7. A large proportion of ancestry-associated CpGs (59%) had a nearby methylation quantitative trait locus (meQTL) and we show that at least 13% of the ancestry-associated methylation patterns were mediated through local genotype. These combined results indicate that ancestry-associated methylation patterns in blood are in large part genetically determined. Our results, further suggest that DNA methylation patterns in blood cells are robust to environmental exposures, at least during the first 7 years of life.