Differential patterns of DNA cytosine methylation in Central African Hunter-Gatherers

DNA cytosine methylation is an epigenetic phenomenon that influences gene expression. To characterize variation of cytosine methylation across ethnically diverse humans we employed high-throughput bisulfite sequencing of 140,749 targeted regions of genomic DNA, encompassing >400,000 CpG sites, from blood originating from 42 genetically, geographically, and culturally diverse Africans. We observed a statistically significant differential genome-wide pattern of methylation in Central African tropical rainforest hunter-gatherer (CAHG) individuals when compared to other Africans. Further, we observed a significant enrichment of sites differentially methylated in CAHG individuals near genes involved in insulin and IGF1 signaling, glucose, fatty acid, and lipid metabolism, as well as stature and bone growth. This observation is of interest given the previously identified attenuated insulin and IGF1 response in short-statured African CAHG. We validated our experimental results by a targeted bisulfite re-sequencing study of a subset of CpG sites in a larger sample of 24 CAHG and 24 pastoralist Fulani living in Cameroon. Together, these results highlight differential methylation patterns in CAHG influenced by genetic and environmental factors.