DNA methylation patterns are important for establishing cell, tissue, and organism
phenotypes, but little is known about their contribution to natural human variation.
To determine their contribution to variability, we have generated genome-scale DNA
methylation profiles of three human populations (Caucasian-American, African-American,
and Han Chinese-American) and examined the differentially methylated CpG sites. The
distinctly methylated genes identified suggest an influence of DNA methylation on
phenotype differences, such as susceptibility to certain diseases and pathogens, and
response to drugs and environmental agents. DNA methylation differences can be partially
traced back to genetic variation, suggesting that differentially methylated CpG sites
serve as evolutionarily established mediators between the genetic code and phenotypic
variability. Notably, one-third of the DNA methylation differences were not associated
with any genetic variation, suggesting that variation in population-specific sites
takes place at the genetic and epigenetic levels, highlighting the contribution of
epigenetic modification to natural human variation.