Mapping the human epigenetic landscape across three generations: A DNA methylation resource from TMM BirThree
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Transgenerational epigenetic inheritance has been demonstrated in rodent models but not in humans. To address this gap, we established a comprehensive DNA methylation resource derived from 158 three-generation Japanese families. The dataset integrates genome-wide methylation profiles with extensive clinical and lifestyle data. Using targeted bisulfite sequencing, we profiled > 1 million CpG sites across the genome, covering the promoter and gene body regions of > 16,500 annotated genes, in 938 adult peripheral blood and 155 neonatal cord blood samples. To demonstrate the utility of this resource, we performed a representative analysis focusing on the intergenerational impact of maternal and grandmaternal pre-pregnancy smoking. We identified persistent methylation marks in neonates associated with ancestral smoking history, suggesting the potential transgenerational transmission of environmental effects in humans. This multigenerational epigenomic resource provides a valuable foundation for future studies on intergenerational epigenetic mechanisms and their role in shaping human health trajectories.
