Systematic investigation of interindividual variation of DNA methylation in human whole blood

Interindividual genetic variability is well characterised, but we still lack a complete catalogue of loci displaying variable and stable epigenetic patterns.

Here, we report a catalogue of stable and variable interindividual DNA methylation sites in human whole blood by analysing the DNA methylation patterns in 3642 individuals from a representative cohort for the British population using the IlluminaEPIC array. Our results show that 34,972 CpGs display variable methylation levels (VMPs) and 41,216 CpGs display stable methylation. Human whole blood is a widely used tissue in epigenetic research, particularly in Epigenome-Wide Association Studies, due to its accessibility and its ability to provide insights into systemic biological processes and disease mechanisms. This catalogue is a useful resource for interpretation of results when associating epigenetic signals to phenotypes. VMPs are highly enriched in CpG shores, enhancers and intergenic regions and approximately half of the VMPs are under genetic control. Our results also showed that trans mQTL-mCpG pairs (that is a SNP and CpG located > 500bp apart) are often located in the same TAD or connected by chromatin loops. A subset of these VMPs (784) are classified as putative epialleles and there is a link between some of these epialleles located in regulatory regions and gene expression.

Our study provides of a comprehensive and reliable catalogue of CpG sites displaying variable interindividual DNA methylation across the human epigenome.