In a new study published on 3 June in Genome Biology, Gunasekara and colleagues present a new map of epigenetic variation in humans. The new information will potentially allow scientists to test for the epigenetic causes of disease, in addition to their genetic basis.
Researchers once hoped that mapping the human genome would help predict and possibly prevent human disease. But 15 years later, it seems epigenetic regulation plays an equally important role and diseases cannot be predicted based on genes alone.
On a basic level, epigenetic alterations are caused by DNA methylation, which essentially “tags” regions of DNA, and can also be achieved through histone modifications, chromatin remodelling, and microRNA. All of these processes either promote or inhibit gene expression without making structural changes to the DNA itself – and are often triggered by the environment.
Epigenetics can influence a wide variety of illnesses, including cancers and neurodegenerative disorders. And the importance of epigenetics has led to the growth of epigenome-wide association studies (EWAS), alongside genome-wide association studies (GWAS).
However, epigenetics is more difficult to study since epigenetic changes tend to be cell-specific. What this essentially means is that while blood samples can be used to genotype an individual, epigenetic marks in blood DNA may not provide the same clues about epigenetic changes in other parts of the body, such as the brain or heart. And this is partly why progress in epigenetics research is much slower.
So, to speed up the process, scientists from the Baylor College of Medicine and Texas Children’s Hospital in the US have started to create a so-called atlas of epigenetic variation in humans. To do this, the team of researchers led by Prof Robert Waterland performed an unbiased screen to search for human genomic regions where interindividual variations in DNA methylation exist but are not cell or tissue-specific.
They achieved this by focusing only on DNA methylation — the most stable form of epigenetic regulation — or more broadly speaking, special regions of the genome where blood samples can be used to derive epigenetic changes throughout the body.
Changes in DNA methylation often occur during embryonic development and can affect an individual for the rest of life. But even more important here, this type of epigenetic regulation can differ among individuals but remains consistent across all of the different cells and tissues of the body.
The researchers profiled or “mapped” DNA methylation throughout the genome of three tissues — the thyroid, heart and brain — taken from 10 cadavers and discovered nearly 10,000 regions with a previously unrecognized level of molecular individuality in humans, referred to as systemic interindividual variation (CoRSIVs). Moreover, methylation was previously shown to be associated with a range of human diseases in these regions, including obesity, cancer, autism, and Alzheimer’s disease.
Since DNA methylation can silence or activate genes, any disease with a genetic basis is also likely to have an epigenetic basis, says Waterland. Thus, mapping epigenetic variations among humans could potentially improve our understanding of disease processes at an epigenetic level.
(1) Gunasekara, C.J. et al. A genomic atlas of systemic interindividual epigenetic variation in humans. Genome Biology (2019). DOI: 10.1186/s13059-019-1708-1