Genes and Polymorphisms That Predict High Performance

By on May 13, 2021
Human DNA

In a few recent posts, I have explored the way that DNA affects our health and performance. Using sites like SelfDecode (affiliate link), we can learn more about our own bodies, and therefore how to get the most from them.

Essentially, DNA is responsible for producing proteins – the building blocks that form our tissues. While there are over three billion “units” of information in the human genome, and 30,000 genes, only a portion of this code varies from person to person.

See also: DNA Analysis Can Help You Optimize Training and Nutrition: My Experience With SelfDecode

Polymorphisms are variations affecting more than 1% of the population. Single Nucleotide Polymorphisms are those affecting only a single nucleobase. Some of these SNPs appear to predict superior athletic or cognitive performance, as well as certain physical traits or personality characteristics.

Single Nucleotide Polymorphism

Following are some of the more commonly studied SNPs known to impact on performance.



ACTN3 is perhaps the most talked about gene when it comes to athletic performance, especially as it relates to explosive strength (note that genes have names like ACTN3, whereas SNPs have names like rs1815739). The ACTN3 gene, also called “the speed gene,” encodes the protein actinin alpha-3, which is a sarco-meric protein related to the formation of fast twitch muscle fiber, recovery, and “training adaptation.” ACTN3 is expressed preferentially in the fastest, type IIx fiber. The ideal genotype, controlled by the polymorphism R577X, SNP rs1815739, can therefore allow an individual to build more explosive muscle, more easily. We see a disproportionately high number of athletes with this adaptation (study, study). Roughly 18% of the population is completely deficient in actinin alpha-3. This is due to homozygosity for a “premature stop codon” polymorphism. It’s swings and roundabouts, though, as these guys tend to perform better in endurance tasks.


ACE polymorphism

Another gene that gets a lot of attention is the angiotensin-I converting enzyme gene, ACE to its friends. ACE can encourage the formation of a vasoconstrictor (blood vessel narrowing agent) called ANG II, while also degrading the vasodilator bradykinin via action at the bradykinin B2 receptor. ANG II is also a recognized growth factor itself and contributes to hypertrophy.

The ACE gene insertion/deletion (I/D) polymorphism is associated with improved exercise performance and duration. In particular, the insertion allele has been shown repeatedly to correlate with improved endurance-related activity as it corresponds with greater kinin activity (vasodilation). The D-allele meanwhile is related to improved strength-and-power-based performance and is regularly found among elite-level swimmers. This D-allele is also related to greater heart response to training in the left ventricle.

It’s important not to consider genes in isolation. Various polymorphisms relating to the ACE gene can interact in different ways with other variants affecting angiotensin receptors for example, or growth hormone production. This may also explain why some studies have failed to find a connection between ACE and high performance among military recruits, or (study).


The ACE gene D-allele effects appear to be more strongly effective when combined with the Bradykinin type 2 receptor genotype (B2BRK). This genotype is associated with increased hypertrophy following resistance training but NOT increased endurance strength (study). Bradykinin appears to influence skeletal muscle glucose uptake and muscle blood flow (study).

Bioneer Genome

Conversely, the B2R -9 allele appears to be associated with higher skeletal muscle metabolic efficiency, and thus improved endurance athletic performance. This effect is compounded when combined with the ACE I-allele.


Interleukin-15 (IL-15) is an inflammatory cytokine that plays an important role in the immune system, but also in skeletal muscle hypertrophy (reference). Plasma IL-15 levels are also inversely related to fat mass (reference). Interestingly, hypertrophy is seemingly increased among those with the AT heterozygotes genotype of the rs1589241 (study) polymorphism. We see a similar effect in the IL6 gene (study), where the GG genotype and G allele of the -174 IL-6 (rs1800795) polymorphism appears to occur more frequently in power athletes.

(Cytokines are substances produced by specific cells of the immune system and which act on other cells.)


The IGF1 gene encodes insulin-like growth factor-1. This, in turn, is the major mediator of growth hormone stimulated somatic growth. It also mediates a number of GH-independent anabolic responses in a variety of cells.

As with many such genes, IGF1 variants can be more or less impactful depending on a variety of additional genes. For example, the gene interleukin-6 (IL-6), its receptor IL6R gene, and IGF-binding protein-3 (IGFBP3).

Ultimately, variations in the IGF1 gene have been found to impact on both maximal force production, anabolism, neurotrophy (the growth of neural tissue), and body fat.


IL-6 polymorphism

Interleukin-6 is a pleiotropic cytokine that also plays a role in fibrogenesis and the expression of vascular endothelial growth factor (VEGF). IL-6 is produced by the muscles in response to exercise and aids in recovery; aiding in neutrophil mobilization and promoting impaired insulin resistance. It is even referred to by some scientists as an “exercise factor.” What’s really interesting, is that IL-6 appears to be particularly useful when engaging in eccentric training and “non-damaging” training, the lengthening portion of a muscle contraction (study, study).


PPARGC1A, or peroxisome proliferator-activated receptor gamma coactivator-1a, is a gene that has been linked in several studies to mitochondrial biogenesis (the process by which cells increase their mitochondrial mass), skeletal muscle metabolism, fatty acid oxidation, glucose utilization, thermogenesis, and angiogenesis (the formation of new blood vessels – a profound and often overlooked contributor to overall muscle plasticity).

This polymorphisms of this gene have been the focus of many studies looking for links between genotypes and athletic performance (study, study). Again, though, it appears as though the most profound effects occur when the most desirable variations occur alongside preferable ACE and ACTN3 genotypes.

Genes for Success and Brain Function

As well as increased speed, strength, and stamina, winning the genetic lottery can also gift an individual with improved cognition (study). For instance, the rs6265 polymorphism affects the BDNF gene. This is brain-derived neurotrophic factor, a chemical that promotes the growth of new neurons and synapses. The C allele of this particular SNP is linked with better N-back scores and working memory (study, study), larger amounts of slow-wave sleep (which is possibly linked with greater neural plasticity study), and possibly higher mean intelligence.

BDNF polymorphism

Genes influence personality in countless ways, too. One of the most interesting genes is COMT, which is referred to as the “warrior/worrier” gene. The SNP rs4680 is linked to our ability to break down catecholamine neurotransmitters such as norepinephrine, cortisol, and dopamine. Thus, COMT activity can influence how quickly an individual is able to recover from stressful events. But, of course, this is again contingent in the initial levels of those neurotransmitters among countless other factors (not to mention life experience).

COMT polymorphism

There have even been studies that link specific SNPs to overall success in education and career paths (success).

The Future is Not Set

I should take this opportunity to point out that this does not mean we should judge a person’s potential success on their genetics. Nor is any genotype objectively “better” than any others. Apart from anything else, these findings are more reflective of the traits that society happens to value at any given tmie, rather than any innate gifts or shortcomings in the population. School systems, in particular, are notoriously bad at predicting future greatness. Examples are forthcoming of those that dropped out of school only to be considered geniuses within their fields. Our measures of fluid intelligence are also far from perfect, and of course there are countless environmental factors that can predict overall success.

See also: The Permanent Benefits of Training – Overcoming the Interference Principle

It’s our differences that ultimately allow us to provide value. Leaders are those that go against the grain. The best artistic creations are those that are truly different from what has come before. Genius, moreso than processing speed or memory, is born from unique insight.

Genetic Mutations

MSTN myostatin mutation

Genetic mutations are different. A mutation is a change to the DNA sequence that is considered abnormal or extremely rare – a deviation from the norm. Beneficial mutations are rare by definition, as those changes that are “successful” are likely to make their way into the general population. The most famous mutation as it pertains to athletic performance affects the myostatin (MSTN) gene. Animals and extremely rare humans with a premature stop codon exhibit a myostatin deficiency. As myostatin is known to inhibit muscle growth, this can lead to “double muscling.” The result is superior muscle strength and size, along with increased running speed in whippet dogs. However, it may also be associated with an increased risk of tendon injuries.

Most mutations are harmful, however. Which is why we’re actually more interested in the slightly less exotic polymorphisms. In short, it’s very unlikely you’re an X-Man. Sorry.

The Role of Gene Expression and Training

And, of course, lifestyle and training also plays a huge role. Depending on your starting hand, you might just be able to train your way out of any perceived shortcomings.


Throughout your cells, different genes are “expressed,” resulting in the production of different proteins. This is how a muscle cell can behave differently from a brain cell, despite containing the same DNA. Gene expression is controlled by methylation: a process in which chemicals called methyl groups attach themselves to DNA and thus “block” specific portions from being active. If you imagine that DNA contains the alphabets, methylation allows the body to spell out certain works by crossing out letters. This is epigenetics.

See also: How Your Diet, Exercise and Psychology Affect Genes

What’s cool about this, is that training, diet, and lifestyle factors all contribute to gene expression and methylation. The moment we begin working out, the activity of genes within muscle cells get altered (reference). Something similar occurs in the brain following a bout of learning (study).

Bioneer Training

Another study had women exercise a single leg and then examined gene expression via muscle biopsies. The results showed that over 5,000 sites were altered in the exercised leg (study), while there were no significant changes in the unexercised leg. This shows that gene expression is also “site specific.” Diet is similarly impactful (study), as can everything from stress, to sunlight, to sleep, and much more.

Interestingly, gene expression itself can also be increased or decreased through diet and may itself be more or less mutable depending on genotype (study).

What’s really cool, is that epigenetic changes can actually stick around – and even be passed on to offspring! Your training, or lack thereof, can have a direct impact on the athleticism of your future children – something to consider!

It’s Complicated


If anything, I hope that all of this serves to show just how truly complex we humans are. Every one of your traits is the result of countless contributing factors, both genetic and environmental. I’ve barely scratched the surface and there’s so much here already that we rarely hear in the conversation surrounding muscle building, or athletic performance.

See also: Your Infinite Potential: Marvels of the Human Body

We are so different, that we should be very careful giving generalized advice to any person. A supplement or nootropic that helps one person, may be ineffective or even harmful for someone else. We also see why different people respond better or worse to particular types of training. The key is to keep looking until you find what works for you.

I believe that we all have something unique to offer, and our success really comes down to our ability to express that uniqueness in a way that is genuine and that offers value.

If you found all this interesting and you’d like to learn more about your own DNA and how it might impact your performance, I highly recommend checking out I’ve put a link in the description below and I earn a bit of commission if you follow that and decide to make a purchase.

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About Adam Sinicki

Adam Sinicki, AKA The Bioneer, is a writer, personal trainer, author, entrepreneur, and web developer. I've been writing about health, psychology, and fitness for the past 10+ years and have a fascination with the limits of human performance. When I'm not running my online businesses or training, I love sandwiches, computer games, comics, and hanging out with my family.

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