Part 1: The COMT Gene
Once you have viewed all your 23 and me reports, you can dive in a little deeper, if you like. I'm going to talk about a few extras that don't show up in your report and how they may play a role in your health and wellness.
First a quick overview on how to find your data. You will see a drop-down menu under your name on the top right of the screen. Under that go to "Browse Raw Data". This will pull up a search function. For each of the genes I mention below I will give you an rsID number that you can search. In the example below I searched rs4680 and that pulled up the position for a specific allele of the COMT gene. In case you are wondering the rsID number is a unique label ("rs" followed by a number) used by researchers and databases to identify a specific SNP (Single Nucleotide Polymorphism). It stands for Reference SNP cluster ID and is the naming convention used for most SNPs. A SNP is just a position in the genome. Each SNP represents a difference in a single DNA building block, called a nucleotide. Most SNPs have no effect on health or development. Some of these genetic differences, however, have proven to be very important in the study of human health. SNPs help predict an individual’s response to certain drugs, susceptibility to environmental factors such as toxins, and risk of developing diseases. Now let's dive into a few interesting areas of the genome that isn't in your standard 23 and me report.
COMT "The Warrior or Worrier Gene"
Catechol-O-methyltransferase (COMT) is one of two major enzymes responsible for catecholamine (a specific type of molecule that includes dopamine, norepinephrine, estrogen, etc.) production and breakdown. The COMT gene is well expressed across the brain and regulates dopamine signaling in the prefrontal cortex. COMT variants can be used as molecular genetic markers associated with anxiety, pain, and stress responsiveness. The most common variant was found to be defined by an amino acid substitution of methionine (Met) in place of valine (Val) at position 158 (Val158Met). Depending on your gene copy number, you could be classed as a worrier (A genotype), a warrior (G genotype), or a mix of the two (AG genotype). An estimated 20-30% of Caucasians of European ancestry have a the COMT gene variation which limits the body's ability to remove catechols by 3-4 times. COMT is also associated with greater levels of cortisol and HPA axis dysfunction (which is largely responsible for the body's ability to calm itself and de-stress).
Because of the effects that COMT has on hormones, it directly affects stress reactivity, health, and well-being. Interestingly, those with this gene appear to experience both negative and positive emotions more strongly. For example, those with the COMT gene variation Met/Met tend to be more neurotic and have lower stress resiliency. However, in one study, people with the Met/Met variation generated almost similar amounts of positive emotion in response to a "bit pleasant event" as people with the no variation (Val/Val) did from a "very pleasant event."
The Warrior Genotype
Warriors genotype traits:
Perform better under stress
Exhibit greater emotional resiliency
Have lower anxiety
Lower attention span
A recent article in The Journal of Sports Science and Medicine found that elite mixed martial arts athletes possess the warrior genotype of the COMT gene when compared to the non-athlete control group. This variant confers resilience to stress as well as an emotional advantage over individuals with the worrier genotype. Additionally, this genotype also confers protection against anxiety and pain susceptibility in these individuals, providing the perfect combination of traits to engage in combat sports.
One study looking at the influence of COMT genotype on measures of perceived pain and state/trait anxiety found that warriors secreted lower amounts of a stress marker in their saliva during stressful situations and that the warrior allele affords an emotional advantage relative to worrier allele carriers.
Surprisingly, having the warrior genotype has other advantageous benefits, such as having more empathy, prosocial behavior, and the ability to process unpleasant stimuli. However, people with this variant were worse in memory and attention tasks when compared to their worrier counterparts.
Are there benefits to having this variant if you aren't an MMA fighter? Yes, of course. The benefits of having this allele can be helpful in the workplace and in life in general, especially given the amount of stress our daily lives contain in 2022. It has been observed that "warriors" thrive in stressful working environments that require a high level of performance, like doctors, lawyers, and CEOs. They are especially emotionally resilient and work well under pressure.
The Worrier Genotype
Worrier genotype traits:
Heightened cognitive performance
Sustained attention
Greater anxiety and stress
Harm avoidance > novelty seeking
According to this Nature study, the worrier genotype of the COMT gene has been characterized as having heightened cognitive performance at the cost of greater levels of anxiety and vulnerability to stress. In other words, these individuals have better short-term memory, sustained attention, and perform better in several tasks, however, this heightened performance is met with significant anxiety and elevated stress response.
When assessing fear processing in these individuals, one study found that the worriers exhibited a significantly heightened startle reflex compared with the warriors, and gravitated toward harm avoidance, as opposed to novelty-seeking, as observed with the warrior genotype.
Further, it was observed that worriers were relatively vulnerable to adversity but responsive to constructive leadership in the working environment. The propensity for worriers to feel stressed doesn’t mean that they should avoid all stressful activities, though. In college students, those that were classed as worriers had significantly higher resilience when compared to their warrior counterparts, which combined with other evidence, suggests that these individuals need low, gradual exposure to a task and should take time to acclimate to the pressure through experience. In other words, consistent exposure to a stressful task will see these individuals excel.
The "Worrier" should avoid stress whenever possible. This COMT gene variation limits the body's ability to remove some stress hormones by 3-4 times. So stress feels stronger, lasts longer, and does more damage. So if you have this genotype be sure to practice stress reduction and self-care.
Nutritional factors that could affect COMT activity
Since the COMT enzyme works differently in the worriers vs. warriors, certain dietary or lifestyle modifications can be incorporated to benefit your genotype to ensure optimal cognitive performance.
For example, if you’re a worrier you may be more sensitive to wine, coffee, and green and black tea. This is because they contain catechols that can affect dopamine production in the brain, which could increase feelings of anxiety. Therefore, reducing your intake of these catechols could be beneficial in that regard. Limiting caffeine can also be helpful, as caffeine can trigger the release of catechols. Limiting alcohol is beneficial since alcohol consumption triggers dopamine release.
Warrior genotypes on the other hand should increase their dietary catecholamines to provide a dopamine boost to get through low-pressure, monotonous tasks. These individuals also benefit from high-intensity exercises that have a ‘thrill’ element to them, such as mountain biking, snowboarding, skiing, and mountain biking to name a few.
Because COMT is a methylation gene, it's essential to get adequate B vitamins to support COMT, especially B2, B6, B9, and B12 as well as magnesium.
To support COMT methylation, others suggest people with COMT Met/Met also take SAMe.
A few other things to keep an eye on are exercise and calorie intake.
Exercise requires methylation and increases catechols. So if you have a difficult time methylating because of COMT (or other genes like MTHFR, which are discussed in depth elsewhere), then you might be better off limiting strenuous exercise.
And fasting can increase catechols, which can bog down COMT. So eating regularly and maintaining blood sugar are essential.
The Bottom Line
The COMT gene and its variants, therefore, determine which environments and circumstances we are better equipped to handle by regulating fluctuations in our dopamine levels in response to stress.
This will either group you as a warrior, enabling you to perform at your highest level with pressure, deadlines, and thrills, or as a worrier, enabling you to thrive in low-pressure, quiet environments to work on complex issues for an extended period.
Although there have been links between these variants to several mental conditions, these links are not definitive and include other factors such as sex, environmental inputs, and other gene interactions to develop such conditions. Genes are not the whole story.
For more reading on this topic, also consider reading the warrior gene.
Stayed tuned as I have a blog part 2 coming where I discuss some additional genes found in your 23 and me data that may impact healthspan and longevity.
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