DNA Analysis for Power and Physique Athletes: Part 1
The science of genomics has advanced quickly over the past decade. You can now purchase a direct-to-consumer (DTC) DNA test for ~$100 and have the data analyzed in less than a month. While the price has dropped dramatically and the number of companies offering this service has grown, the interpretation of results for athletes is still at an early stage.
In this series I’ll focus on how genetics and performance interact. Part 1 covers the regulation of tests, important genetic terminology, and the ACTN3 gene.
Outline
- Regulation of tests
- Genetics Overview
- ACTN3 Gene
- My ACNT3 Variant
Regulation of Tests
The Human Genome Project found that humans have between 20,000 and 25,000 genes. The genome project was completed in 2003 and opened the door to a lot of scientific discoveries. Shortly thereafter, companies started taking advantage of the technology for DTC marketing. This prompted the government to step in. First, the US Government Accountability Office (GAO) released a report in 2010 stating that some companies had misleading genetic test results and deceptive marketing with questionable practices. Then the FDA sent out cease and desist letter to 23andMe in 2013. However, in 2015, they approved DTC carrier screens for diseases and later for genetic health risks.
Overall, DNA testing is still poorly regulated. Companies can take tests to market without independent analysis to verify their claims. To date, the only test backed by the FDA is 23andMe. Furthermore, a recent announcement from the FDA warned against modifying medications:
Patients and health care providers should not make changes to a patient’s medication regimen based on the results from genetic tests that claim to predict a patient’s response to specific medications, but are not supported by scientific or clinical evidence to support this use, because doing so may put the patient at risk for potentially serious health consequences.
This leads us to an impasse — what do we make of the genetic tests available? Which one should we use and/or trust? It seems like there’s only one right now that’s vetted and that’s not even for performance purposes. To really answer the question we would need to see data on reliability, validity, and precision from each company selling tests. That probably won’t happen. It also doesn’t help when we see stories of people who submit DNA to two companies and get different results or people who submit DNA to the same company and get different results. That’s why we need to be cautious when interpreting our DNA data. For now it’s fun toy for athletes. In the future it could be more.
Genetics Overview
Before we get too deep into individual genes we need to cover some basic terminology.
- Genes are the basic physical and functional unit of heredity. Genes are made up of DNA. DNA is made up of the nucleotides A, T, C, and G.
- Gene variants are the differences that make a genome unique. We can identify variants by comparing your DNA sequence to the sequence of a reference genome maintained by the Genome Reference Consortium.
- Single nucleotide polymorphisms (SNPs) are gene variations that occur when a single nucleotide differs from the reference genome. For example, a SNP may replace the nucleotide Guanine (G) with the nucleotide cytosine (C) in DNA.
- A variation in the DNA sequence that occurs in a population with a frequency of 1% or higher is termed a polymorphism. A polymorphic variant of a gene can lead to the production of a different form of the protein. When a variant appears in less than 1% of the population, it is considered a mutation.
When reading about variants there are two important things you need to know: RsID and genotype. The rsID number is (“rs” followed by a number) used to identify a specific SNP. It stands for Reference SNP cluster ID and is the naming convention used for most SNPs. For genotype there are two main abbreviations — the (C;C) genotype is often called RR, whereas the (T;T) genotype is often called XX or X. For example, My genotype for the ACTN3 gene is TT, so I would be referred to as R577X — a polymorsphims identifier — because I have two T variants which is tested at rs1815739.
There has been some confusion and controversy in how we define each of the above terms based on what field of study you are in (e.g., biology vs biochemistry). If you want to read more about it check out this.
The era of athlete genomics began in the early 2000s with the discovery of genetic markers associated with athletic performance. Since then there have been a number of genetic variants associated with performance, nutrition, sleep, and supplements.
ACTN3
In 1999, a common polymorphism was identified in ACTN3 [R577X] that results in absence of α-actinin-3 in more than one billion people worldwide, despite the ACTN3 gene being highly conserved during human evolution (North et al., 1999). Interestingly, it was discovered serendipitously while searching for possible causative genes for muscular dystrophy.
ACTN3 is one of the first and most common genetic markers associated with athletic performance (Webborn 2015). The ACTN3 gene encodes the protein alpha-actinin-3, a sarcomeric protein that is a primary component of the Z line in skeletal muscle fibers. The Z line is a structure within the sarcomere and functions to provide support for the transmission of force when muscle fibres are activated (Wilmore 2004). Alpha-actinin-3 forms a lattice structure that anchors together actin filaments and stabilizes the muscle contractile apparatus. ACTN3 is expressed in fast, type II fibers, where it plays an important role in the generation of explosive and powerful muscle contractions.
One of the most commonly cited research papers to support genetic testing in sports is a 2003 study of the ACTN3 genes in elite-level sprinters (Yang et al., 2003) and it has been highly studied since then in several athletic populations.
In a study on bodybuilders, powerlifters, and other strength athletes there was a low proportion of the ACTN3 R577X genotype (Roth et al., 2009). Earlier, in a study on competitive Russian power athletes, there was also a lower proportion of the ACTN3 R577X genotype with the lowest frequency found in a group of highly elite athletes (Druzhevskaya et al., 2008). A recent meta-analysis found associations between the RR and RX genotypes and elite power athlete status (Tharabenjasin et al., 2019). Taken together, if you have the ACTN3 R577X genotype you are less likely to be an elite strength/power athletes and if you have the RX or RR genotype you may be better suited for strength and power sports. On the other hand, there is literature supporting that people who have the R577X genotype are better at endurance sports (Lee et al., 2016).
There is some evidence to suggest that those with the RR genotype can adapt better to resistance training. Two studies reported that the RR genotype was associated with the greatest increase in strength (Pereira et al., 2013) and power (Delmonico et al., 2007) following resistance training. However, another study reported no effect of ACTN3 genotype on training adaptations following resistance training (Erskine et al., 2014). The underlying mechanism between genotypes could act through differential mammalian target of rapamycin (mTOR) and p70S6k phosphorylation since the RR genotypes are phosphorylated more than XX genotypes, indicating a less pronounced activation of hypertrophy signaling in XX (Norman et al., 2014). Ultimately, it’s still unclear if there is any benefit of genotype on adaptation potential, but it would make since if it did limit adaptation since there are a lower proportion of the XX genotype in elite athletes.
ACTN3 Summary
There is a strong impact of genetics on both performance and exercise adaptation. One of the most well-studied of those is ACTN3, which is more prevalent (RR genotype) in high level strength and power athletes. Furthermore, mechanistic findings support alpha-actinin-3 has a beneficial effect on the function of skeletal muscle in generating forceful contractions at high velocity. Some research suggests it may also influence training adaptations. It’s important to remember that this genotype will not prevent you from adapting to training, you may just be less likely to be an elite power/strength athlete if you have it.
My Variants
I’m a R577X genotype, which means I lack the alpha-actinin-3 protein in my muscle.
I’ve never been fast or explosive. In sports (soccer/football) I was more of a control player that utilized my technical skills, positioning, and intelligence to succeed. I’m also not great at powerlifting or weightlifting. Seeing this result mainly confirms what I already knew — I’m probably not meant to be elite in strength and power sports… and I’m okay with that.
Additional Resources for ACTN3
A blog by one of the authors from Yang et al., 2003 the can be found here.
Genetic Markers Associated with Power Athlete Status
Genetics and sport performance: current challenges and directions to the future
