Population-specificity of human DNA methylation

Area of Science:

• Genomics
• Epigenetics
• Population Genetics

Background:

• Ethnic differences in DNA methylation are known for specific sites.
• Genome-wide patterns and extent of these differences remain largely unknown.
• Population-specific genetic control of DNA methylation has not been investigated.

Purpose of the Study:

• To investigate genome-wide DNA methylation patterns across different human populations.
• To determine if the genetic control of DNA methylation is population-specific.

Main Methods:

• Measured DNA methylation near transcription start sites of over 14,000 genes in cell lines from African and European populations.
• Analyzed heritability of DNA methylation at CpG sites.
• Performed genetic mapping of DNA methylation and validated findings in brain samples.

Main Results:

• Found population-specific DNA methylation patterns in over one-third of all genes studied.
• Identified heritable DNA methylation at over a thousand CpG sites, with differing heritability between populations.
• Demonstrated that divergence in allele frequencies largely explains population specificity in genetic control of DNA methylation, with limited overlap between populations.

Conclusions:

• DNA methylation exhibits significant divergence between human populations.
• This divergence is attributed to differences in allele frequencies and potentially complex epistasis or gene × environment interactions.