We next analyzed the enrichment or depletion of replicated disease-specific GWAS variants in fetal stage DHSs relative to the proportion of total GWAS SNPs in these DHSs. We found the greatest enrichment in phenotypes for which gestational exposures or growth trajectory have been shown to play major roles, including menarche, cardiovascular disease, and body mass index (Fig. 1E) (14, 16). By contrast, we observed relative depletion in fetal DHSs of aging-related diseases, cancer, and inflammatory disorders with presumed (postnatal) environmental triggers. These findings suggest a recurring connection between an exposure-responsive gestational chromatin landscape, regulatory genotype, and risk for specific classes of adult diseases and traits.
