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A map of human individuality

A great body of research into the human epigenome has focused on cell type-specific, dynamic DNA methylation patterns. Now, a study in Genome Biology reports an atlas of systemic interindividual epigenetic variation, that is, DNA methylation that is consistent across tissues and cell types but varies between individuals. It highlights these genomic regions as a source of phenotypic variation in humans that correlates with gene expression and is associated with disease.

Credit: marcos alvarado/Alamy

The team measured CpG methylation by deep whole-genome bisulfite sequencing of genomic DNA from thyroid (representing endoderm), heart (representing mesoderm) and brain (representing ectoderm) samples obtained from ten donors as part of the Genotype–Tissue Expression (GTEx) programme. This screen identified 9,926 correlated regions of systemic interindividual variation (CoRSIVs), that is, regions containing at least five CpGs at which epigenetic variation between individuals (interindividual methylation range of ≥20%) was consistent across all three tissue types. Although comprising only ~0.1% of the human genome, CoRSIVs are intercorrelated over long genomic distances, which suggests links to genome organization.

The authors used four complementary approaches to evaluate the extent to which DNA methylation at CoRSIVs is genetically mediated. These analyses revealed that ~60% of interindividual variation in CoRSIV methylation could be explained by cis regulatory variation, while ~40% showed no underlying genetic effect, although trans effects cannot be ruled out.

Importantly, DNA methylation in adipose tissue correlated with gene expression in not only the same tissue but also across two types of other tissue (skin and lymphoblastoid cells) for 645 gene-associated CoRSIVs, as determined by analysing a previous large-scale population data set. This finding suggests that CoRSIVs identified from easily obtainable sources, such as peripheral blood, could be used to infer epigenetic regulation in difficult to access tissues, such as brain, for example.

“This map … provides new targets for studying the link between development, epigenetics and disease”

Finally, analysis of 1,319 epigenome-wide association studies based on DNA methylation showed a 37% enrichment for disease-associated CpG sites in CoRSIVs compared with control regions. CoRSIVs were not enriched for cancer but exhibited strong associations with non-cancer diseases, including several disorders related to immune function. This map of stable interindividual epigenetic variation provides new targets for studying the link between development, epigenetics and disease.


Original article

  1. Gunasekara, C. J. et al. A genomic atlas of systemic interindividual epigenetic variation in humans. Genome Biol. 20, 105 (2019)

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Further reading

  1. Taudt, A., Colomé-Tatché, M. & Johannes, F. Genetic sources of population epigenomic variation. Nat. Rev. Genet. 17, 319–332 (2016)

    CAS  Article  Google Scholar 

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Correspondence to Linda Koch.

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Koch, L. A map of human individuality. Nat Rev Genet 20, 435 (2019).

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