Genetic testing alone can’t tell you your real risk of disease.
Written by: Emily Lind
Medically reviewed by: Rob Philibert, MD PhD
There is an overwhelming number of genetic testing services available, all of which claim to give you important information about your health. But how much can they really help you?
The limits of genetics for predicting disease:
Most people know that their genes are the instruction manual for the entire body. The genome contains all the information required to make proteins, hormones, and more. Certain variations or mutations in genes can cause different traits, or ‘phenotypes’ to be present. However, having certain mutations does not always guarantee certain traits, diseases, or behaviors.
Take for example identical twins who share the same genes. You’d expect them both to have the exact same traits and diseases, but this isn’t always the case. If one twin has schizophrenia, the other twin will only have the disorder 50% of the time. Other factors like rheumatoid arthritis, diabetes, breast cancer, and Crohn’s disease seem to be more determined by environmental influence rather than genetics. In other words, nurture can cause disease states even when nature (genetics) are the same.
How can we look at the impact of the environment on our health?
The reason why two identical twins don’t have the same propensity for disease is complicated, but a lot of the variability comes down to epigenetics. ‘Epi’ is a Greek word to mean ‘above,’ so epigenetics means things that are above genes, controlling when they are turned on or off.
| Genetics | Epigenetics |
| Does not change | Changes in response to the environment, age, and more |
| Instructions (genes) for all proteins and cell functions | Controls which genes are turned on/off in different tissues, disease states, etc. |
| Propensity for a disease/trait | How you compare to other people with the same genetic propensity |
The fascinating thing about epigenetics is that while genetic variation doesn’t change, epigenetic signatures are constantly changing. For example, epigenetics controls the different functions of your organs and tissues. Nerve cells and muscle cells have the same DNA but work completely differently. Epigenetics is what turns ‘on’ genes to make muscle-specific proteins, and also turns ‘off’ proteins needed in other cell types. Epigenetics also changes with age – the genes that are turned on or off in a 26-year old are very different from the genes that are turned on in a 100-year old, or a newborn.
How do epigenetics work?
There are several ways that epigenetics work to control gene expression, including histone modification and non-coding RNA. For now, we’re going to focus on DNA methylation because it is the easiest to measure. This type of epigenetic modification works by adding methyl groups (CH3) to DNA at specific adenine or cytosine nucleotides. When a gene is turned on, complex cellular machinery can latch onto the gene, read DNA and use it as the instructions to build a specific protein.
When a methylation is in place near where the protein-building machine starts reading, the machine can’t latch on to read the genes. This means that once the methyl group is attached, the gene can’t be expressed as a protein. What makes DNA methylation useful for cells is that the methyl groups can be taken off the gene or put back on at any time in response to changes in the cellular environment. This lets the protein production of the cell be very carefully controlled.
Image adapted from National Cancer Center Research Institute.
Epigenetics and health
DNA methylation allows cells to carefully control how and when genes are turned on and how much proteins are produced. However, lifestyle and environmental factors can cause dangerous changes to normal epigenetic function, leading to many different diseases. For example, epigenetic dysregulation is associated with atherosclerosis, which can lead to heart attack, stroke and death. Epigenetic dysregulation also influences other cardiovascular disease risk factors like diabetes, stress, and nutrition.
The good thing is that unlike genetics, which only tell you your propensity for a disease, epigenetics can also show you if your risk of disease is improving. Take smoking for example. Heavy smokers have decreased methylation of the AHRR and CSKSR1 genes than non-smokers, which is associated with higher risk of lung cancer and atherosclerosis. After quitting smoking, methylation levels begin to return to normal levels. This can help to decrease their risk of lung cancer and heart disease.
How can I monitor my epigenetic health?
Epigenetic testing is a new field, but there are some options available to Americans. One useful tool is the Epi+Gen CHD test by Cardio Diagnostics Inc., available through Elicity. This powerful test recently won Clinical Diagnostics Solution of the Year.
Epi+Gen CHD monitors five common genetic mutations associated with heart disease, giving you a baseline understanding of whether your genes put you at risk. Where Epi+Gen CHD differs from other genetic testing options is that it also provides epigenetic information for three critical DNA methylation sites.
This combined epigenetic/genetic approach allows for Epi+Gen CHD to better predict your 3-year risk of CVD than the standard lipid tests offered by most doctors. Even better, Epi+Gen CHD is accessible in the comfort of your own home through telemedicine appointments with doctors. It’s never been easier to understand your real risk level for heart disease.
Resources:
- https://learn.genetics.utah.edu/content/epigenetics/twins/
- https://www.genome.gov/genetics-glossary/Epigenetics
- https://www.cdc.gov/genomics/disease/epigenetics.htm
- https://www.nature.com/scitable/topicpage/the-role-of-methylation-in-gene-expression-1070/
- https://www.nhlbi.nih.gov/health-topics/atherosclerosis#:~:text=Over%20time%2C%20plaque%20hardens%20and,%2C%20stroke%2C%20or%20even%20death.
- https://www.mdpi.com/2227-9717/9/4/699/pdf
- https://elicity.health/our-tests/details/heart-disease-risk
- https://cardiodiagnosticsinc.com/biotech-breakthrough-award-press-release/
- https://www.futuremedicine.com/doi/10.2217/epi-2021-0123