Multigenerational epigenetic inheritance in humans: DNA methylation changes associated with maternal exposure to lead can be transmitted to the grandchildren

We report that the DNA methylation profile of a child’s neonatal whole blood can be significantly influenced by his or her mother’s neonatal blood lead levels (BLL). We recruited 35 mother-infant pairs in Detroit and measured the whole blood lead (Pb) levels and DNA methylation levels at over 450,000 loci from current blood and neonatal blood from both the mother and the child. We found that mothers with high neonatal BLL correlate with altered DNA methylation at 564 loci in their children’s neonatal blood. Our results suggest that Pb exposure during pregnancy affects the DNA methylation status of the fetal germ cells, which leads to altered DNA methylation in grandchildren’s neonatal dried blood spots. This is the first demonstration that an environmental exposure in pregnant mothers can have an epigenetic effect on the DNA methylation pattern in the grandchildren. For the study, we selected 35 dried blood spots (DBS) collected from mother-infant pairs from Health Fairs ran in three Detroit communities, because they have a high prevalence (8-11%) of high BLL in children. The sample set consisted of 25 male children and 18 female children. We also collected the neonatal DBS and mother neonatal DBS for these mother-infant pairs from the Michigan Neonatal Biobank. Then we measured a blood lead levels in dried blood spots using using atomic absorbtion spectrophotometry. Finally we measured the DNA methylation levels using human methylation 450K array from Illumina. Then we normalized the data for technical biases and tried to infer the the locus specific DNA methylation changes due to Pb exposure which was carried over from the grandmothers to the grandchildren by the Pb –exposed fetal germ cells of the mother using statistical model proposed by Sofer et al, 2012.