Genes Are Informative, Not Deterministic.
Genes should inform your decisions, they should not determine your life. Our genes should guide behavior so that we can mitigate risks of developing certain illnesses. Many scientists believe that genes encompass 20% of who we are, while our daily choices, actions, and environment compose the other 80%.
We have come very far since the 2003 Human Genome Project, when the genome was first sequenced. Although we know a lot about genes, there is still much left to be discovered. To make this point, humans share 99.9% of genes with mice, but we are far different from our furry friends. Genes don’t tell the whole story.
Background & Epigenetics:
The concept of epigenetics makes clear that we are much more than a series of genes. Epigenetics explains how external factors affect how and which genes are expressed. Though we contain 25,000 genes, only a fraction are actually expressed. Further, even if you have a gene for a disease, like the BRCA gene (gene for breast cancer), you are only ~70% likely to get the disease (1). Clearly, many factors beyond our genes affect health outcomes.
Still, by understanding genetics, we gain important and actionable knowledge. Genes dictate how proteins and enzymes are produced within the body. These proteins are the building blocks of life, and enzymes dictate our functionality. Therefore, by knowing our genotypes, we can understand how our bodies operate and steps to take to optimize function. By knowing genetic risks, we can guide how we live our lives and take preventive measures.
For these important reasons (and many more), we offer genetic testing to our patients when deemed helpful.
Why Genetic Testing is Important:
1. Genes can dictate your response to medications.
To illustrate this point, let’s look at the CYP2D6 gene. This gene tells us how well we metabolize SSRIs (selective serotonin reuptake inhibitors). Different variants of this gene can cause you to rapidly or slowly break down SSRIs, resulting in either excessively high or low concentrations of SSRIs in the blood. If you break down SSRIs slowly, you’ll have higher concentrations in your blood, and can therefore experience worse side effects (2).
Another example of how our liver metabolism genes can dictate our response to medications is the SLCO1B1 gene, which can affect response to statins. Depending on the variant of SLCO1B1 gene, you can be at high risk for developing statin-induced myopathy (muscle pain and injury) when taking statins (3).
Perhaps surprisingly, it is not standard of care to test genes before pulling out the prescription pad. SSRI’s and statins are among the most frequently prescribed medications, and yet, most doctors do not screen for genetic variants. Conversely, at PrimeHealth, we take genetic factors into account when creating your Personalized Wellness Plan.
2. Genes can dictate how you handle stress.
Under stress, the body enters the “fight or flight” response, releasing catecholamine neurotransmitters like epinephrine, norepinephrine, and dopamine. This can be useful; it pushes blood to the limbs in preparation for quick movement. Dopamine and norepinephrine also increase focus and concentration. So far, so good. However, if these neurotransmitters are in excess, they cause anxiety.
To understand how your genes affect the stress response, let’s consider the COMT gene. The COMT gene creates the COMT enzyme, which breaks down epinephrine, norepinephrine, and dopamine via methylation. If you have two A alleles of this gene, the COMT enzyme is less active and creates less COMT enzyme. This means less neurotransmitter is broken down and you’re considered a “worrier”. The result of the two A alleles is a higher concentration of dopamine and norepinephrine in the prefrontal cortex. While this does have advantages (ie: more creativity, improved reading comprehension, and more), it can be troublesome. It can mean being prone to depression and anxiety, less emotional resilience, and less empathy and cooperation. Conversely, the G/G allele type is associated with higher COMT activity, and therefore, faster breakdown of norepinephrine and dopamine in the prefrontal cortex. Those with the G/G allele are often referred to as “warrier” types, and can usually better handle stress, have improved working memory, are more cooperative and empathic, and have higher emotional resilience.
Genes are not just one or the other – we are often a mix of both parents. If you receive one A allele from your father, and one G allele from your mother, then you are a mix. In this case, on average, you would show a mix of the characteristic associated with those that are A/A and those that are G/G.
At PrimeHealth, we make specific recommendations on supplements and lifestyle choices to help balance your COMT genes. For example, to improve focus and concentration for a G/G genotype, we may recommend green tea, as the EGCG in green tea is a COMT inhibitor, and can increase dopamine and norepinephrine in the brain.
3. Genes can impact your predisposition to breast cancer.
Having the BRCA1 and BRCA2 gene can mean a ~70% chance of developing breast cancer before age 80. However, most are unaware that the COMT enzyme is also involved in estrogen metabolism, with possible links to breast cancer (4). In addition to impacting neurotransmitters, the COMT gene also methylates catechol-estrogens, deeming them inactive and less likely to lead to breast cancer. Therefore, if you have a more active COMT enzyme (the G/G genotype), you may have less risk of breast cancer and other estrogen-related diseases. If you have the “worrier” or A/A genotype, then you may be at higher risk. Knowing this, we can mitigate risk by making sure your methylation pathways are functioning appropriately. This is accomplished checking homocysteine levels, and ensuring optimal vitamin B12 and folate levels. By doing so, we help estrogen to be methylated properly and disposed of in an optimal way.
4. Certain genes highlight increased risk of Alzheimer’s disease.
We have been hearing more about the ApoE gene and its relation to Alzheimer’s disease recently, as Alzheimer’s is now the 6th leading cause of death in the U.S. By knowing your risk, you can use lifestyle interventions to hopefully prevent disease. There are three ApoE variants: ApoE2, ApoE3 and ApoE4. If lucky enough to have two copies of the ApoE2 variant, the risk of developing Alzheimer’s is 20% less than average. Two copies of ApoE3 gives you an average risk, while two copies of ApoE4 is estimated to mean an almost 10-fold increase in risk to develop Alzheimer’s. Additionally, there are other, less known genes that are involved in the development of Alzheimer’s. These genes code for the proteins presenilin 1, presenilin 2, and amyloid precursor protein. Though the prevalence of mutations in these genes is very low, mutations can lead to early-onset of the disease, around ages 40-50. If you have a close family member with early-onset dementia, it may be worth looking into genetic tests for yourself.
Alzheimer’s prevention research is becoming more robust, especially research from Cornell University (led by Dr. Richard Isaacson), and Dr. Dale Bredesen’s research in San Diego. Two essential interventions that I advise everyone do to prevent Alzheimer’s disease is to exercise regularly (5,6) and eat an anti-inflammatory diet full of turmeric (7). These are topics that we discuss in detail with each patients at PrimeHealth.
5. Your genes can tell you what type of exercise is optimal for you (8).
This testing is available directly through DNAfit. Their genetic report includes information about whether to focus on endurance vs. power training, your aerobic potential, post-exercise recovery ability, the best nutrition for recovery, and risk of injury. What’s more, the effect of each gene is supported by at least 3 peer-reviewed human studies.
For example, to evaluate whether endurance or power training is best for you, they look at a gene that codes for the bradykinin receptor B2 (BDKRB2). If you have the T/T version of this gene, you should respond better to endurance training than those with the C/C version. They also look at the ACE and ACTN3 genes; if you have the I/I and the R/R genotypes, you will likely benefit from endurance training over power training (9).
6. The MTHFR gene gives us a clue about how well we methylate.
The MTHFR gene receives a lot of attention due because certain variations of this gene affect ~10% of the US population. This gene codes for the MTHFR enzyme, which is critical for methylation reactions. Methylation is an essential reaction that occurs every moment. Methylation is involved in activating and deactivating genes, making neurotransmitters, detox, and hormone and fat metabolism. Having two copies of the C677T variant can make your MTHFR enzyme up to ~70% less active than “normal”. If this is the case, you will likely benefit from taking methylation factors like methyl-B12, methyl-folate, SAME-e, niacin, vitamin B6, and TMG. Broccoli, avocado, brussels sprouts, green leafy veggies, and grass-fed organic meats are great dietary sources of methylation factors.
Information about genetics and their affect on functionality is vast, and growing larger. This information is useful for creating an environment that supports long-term health optimization. That said, don’t get too caught up in your genes; they are only 20% of the story. What’s most important is what we do with this information and how we live our lives. If you’d like support navigating your genetics, working with a healthcare provider certainly helps. Luckily, though, you can make many choices on your own to help you live a healthy life.
- JAMA. 2017 Jun 20;317(23):2402-2416 (https://www.ncbi.nlm.nih.gov/pubmed/28632866)
- Clin Pharmacol Ther. 2015 Aug;98(2):127-34. (https://www.ncbi.nlm.nih.gov/pubmed/25974703)
- Diabetes Care. 2013 Aug; 36(Suppl 2): S325–S330. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3920796/
- Toxicological Sciences, Volume 81, Issue 2, October 2004, Pages 316–324 (https://doi.org/10.1093/toxsci/kfh216
- J Clin Neurol. 2015 Jul;11(3):212-219.
- Science 07 Sep 2018: Vol. 361, Issue 6406, eaan8821
- The American Journal of Geriatric Psychiatry Volume 26, Issue 3, March 2018, Pages 266-277
- Med Sport Sci. 2009;54:43-71. doi: 10.1159/000235696. Epub 2009 Aug 17.
- The Association of Sport Performance with ACE and ACTN3Genetic Polymorphisms: A Systematic Review and Meta-Analysis. PLoS One. 2013; 8(1): e54685. Published online 2013 Jan 24.