Calculation of Specific Disease risks
Epigenetic changes, such as differences in DNA methylation, histone modifications, and changes in non-coding RNA functions, are associated with many disease pathologies, including the major age-associated diseases. While future research is still needed to decipher which modifications are causative versus being a by-product of molecular damage, the presence of diseases or the risk of developing them can be detected using epigenetic testing.
Cancer was the first disease to be linked to epigenetics, with a loss of genome-wide DNA methylation being observed in many cancers. The loss of DNA methylation can lead to genome instability as well as tumor growth due to the expression of normally silent, growth-promoting genes. On the other hand, increased DNA methylation was found for specific genes, many of which are in the group of the so-called tumor suppressor genes. Tumour suppressors are required for the healthy functioning of cells. Some of them are involved in DNA repair, while others slow down cell division and make sure that cells die when their time comes. Thus, it is easy to imagine how their absence can lead to cancerous states, and indeed, epigenetic silencing of tumor suppressor genes via DNA methylation is often the first sign of cancer.
Epigenetic modifications are also prevalent in Type 2 Diabetes. A Genome-wide DNA methylation analysis found almost 850 genes with altered DNA methylation profiles in pancreatic islets of diabetic patients as opposed to healthy individuals. Some of these genes, such as CDKN1A and PDE7B, were shown to be directly involved in the manifestations of diabetes.
The overexpression of the latter genes was observed in diabetic patients, resulting in the decreased production of insulin when stimulated with glucose. As for neurodegenerative diseases, a genome-wide association study in Alzheimer’s patients found more than 1200 DNA regions that are differently methylated than in healthy individuals. While the loss of DNA methylation is a normal by-product of aging, its rate seems to be accelerated in Alzheimer’s patients. One of the main physiological manifestations of Alzheimer’s disease is the presence of β-amyloid plaques in the brain. A candidate gene from the study, DSCAML1, was shown to increase plaque formation when demethylated, as it enhances the production of BACE1, a key component in plaque formation.
- Cardiovascular Disease Risk 47% 47%
- Alzheimer’s Risk: 77% 77%
- Dementia Risk 68% 68%
- Type-2 Diabetes Risk 23% 23%
- Lung Cancer Risk 34% 34%
- Breast Cancer Risk 12% 12%
- Brain Cancer 26% 26%
- Colorectal Cancer Risk 41% 41%
Further examples of genes involved in the epigenetic manifestations of disease are endless. Epigenetic testing has been in use for a couple of years now for the early detection of diseases, calculating their risks, and even establishing disease prognosis. DNA methylation-based biomarkers are more and more available and highly sensitive; some tests can even detect a single methylated allele among 50,000 non-methylated ones. Thus, epigenetic testing is expected to revolutionize precision health and life insurance calculations with regards to detecting and treating age-associated diseases. Our models at EPIGEN use the most comprehensive bioinformatic models to make risk calculations exact.