Genetic Testing for Sports Performance

**Andy Galpin** (0:00)
The science and practice of enhancing human performance for sport, play and life. Welcome to Perform. Hello again, friends. I'm Dr. Andy Galpin. I'm a professor of kinesiology in the Center for Sport Performance at Cal State Fullerton. Today, we're gonna be talking about the role of genetics in human performance. Now, scientifically, this is referred to as sports genomics. Now, this field can be broken up in two main areas. The first is really what we call descriptive or talent identification. This is things like, can you use genetic testing to determine what sports you'll be best in? You'll have more success in soccer or baseball or football or hockey or whatever else. Another example of that would be, can we separate the best from the rest here? Are there any genetic markers that can be found in people that will tell us who's gonna be a world champion versus just international level or national level or maybe even not good? Other areas within this descriptive or talent ID are things like your physical attributes. So what genetic markers are available that tell us who's gonna be stronger and why, have better endurance, higher VO2 max, more lean muscle mass and other general physical attributes. And then finally, there's other things such as recovery from injury, who's more resilient to concussions, who's gonna be less likely to have soft tissue damage, and other things that will either put us on the shelf or help us come back from these injuries faster. An excellent example of this is the classic story of a world champion Finnish cross-country skier named Eero Montoranta. Now I apologize on the name pronunciation there. But nonetheless, Eero was a multiple time world champion, I believe even won three gold medals in cross-country skiing in the early 1960s and 70s. Now what was crazy about Eero is people were convinced he was cheating somehow. Remember this is back in the 1960s and 70s, and testing wasn't that available or extensive. And no one really found any evidence that he was cheating, although side note, he actually was taking amphetamines, but they were legal at the time, I think. But nonetheless, the point is why people thought he was doing something odd, it was because his hematocrit and hemoglobin levels were off the chart. Now in another episode of this podcast, we go into detail about the cardiovascular system and what those metrics are. But very briefly, you can think about your hematocrit as how many red blood cells you have in your body, and your hemoglobin is a similar metric. And what was crazy is his hemoglobin was somewhere between 20 and 24 grams per deciliter. The average person is more like 14 or 15 So this was off the charts. His hematocrit was over 60%. Most high level athletes are going to be in the upper 40s, maybe low 50s. And so they had the metrics that were standardized at that time, completely off the charts. And he's out there winning race after race. And so people were convinced he was cheating or doping using EPO or something like that. Well, it turns out he wasn't doing any of those things. We didn't actually know that, though, for almost 25 years later, until 1993, where a geneticist came along, tested him, and identified he had an extremely rare mutation that made his EPO receptors incredibly sensitive. And so when people tested him for his EPO concentrations, they were normal. It just happened to be his receptors were hypersensitive to his training, and so thus he was a mega responder to that, was able to have a hematocrit and hemoglobin concentrations that would honestly probably put most of us in the hospital or dead. And it actually went to his advantage and enabled him to perform at an exceptionally high level. They're actually are somewhat reports though, I'm not sure if they are confirmed, his family had the similar mutation. And so this is why a lot of people think it was actually a very legitimate thing, and he wasn't actually using that as an excuse because it seemed to be persistent among many of his family members as well. And so the idea here is what if markers like this exist? And what if you could find them? What if you're looking for the next talented world record breaking skier or athlete of some sort, and we could see and find markers of superhuman capability? We can make sure these individuals get the resources and training and access they need to really become something special. Or even if it's within yourself, can you identify something about you that makes you unique, that explains why you respond to exercise well, perhaps not as well, and thus maybe need different training, nutrition or other modalities to maximize your performance? Well, that sounds like a pipe dream. Cases like this have existed and are clearly out there. So that would be one example of using sports genomics for talent identification. The second broad category here is what I'll call intervention, which is to say, can you actually get some sort of genetic testing done and then make some sort of change and get more progress based on the information you learn from your genetic profile? This can be done in a lot of different ways, but think about it from the perspective of precision training or precision nutrition. You get a genetic test done and you realize you'll respond better to A type of training or B type of training. Particular supplementation, nutrients, nutrition profiles, eating styles, other things that can happen that will make you respond better and get you faster to your physical and performance goals. From the exercise perspective here, we tend to call this responsiveness. So you want to know which style of training you're going to respond the best to. From the nutrition perspective, we often call it nutrigenomics. So what is the nutrition, optimal nutrition, based on your unique genetic profile? Now the third component here is actually what's called gene doping, therapy or editing. And that is the ability to go in, identify your genetic profile and genome, and then change it to get a certain outcome or response. Now a lot of people have heard about things like this, but they don't really realize, is that actually real? Is it happening? And I can tell you right now, the answer is absolutely yes. There have been over a thousand clinical trials on gene therapy done, and there have been multiple cases and reports of this being used in sporting context. And so this is something that absolutely exists. It's only going to continue to expand in its reach. And I think it's important then for us to understand what is exactly happening here. How is it being used? Is it appropriate? And how we should be thinking about this moving forward. The best example of this was the story of rapoxygen. Now, this was a gene therapy that came out in 2002, not gene editing, but a therapy, a drug. And this was designed actually for anemic folks, and they were trying to enhance the ability of EPO to deliver and utilize oxygen in the body for those that were struggling with red blood cells. Now, this actually was only around for about a year, and I don't think there's any evidence that it ever was put into use in human testing. However, in 2004, there's actually a case of a German track and field coach who was caught and sent into jail for using rep oxygen in his athletes and actually trying to access more of it once it went off the market. And so clearly, I believe this is an area of human performance that we all need to know more about. So if I had to simplify my goal for this entire show, it would be to answer the question about, what do we really know about the current state of genetic testing for performance? An important caveat here, I'm not talking about or will be talking about anything related to disease. The necessity and usefulness and application of genetic testing for various disease states is an entirely different topic. I am a PhD, not an MD. The conclusions and summaries and data that we bring about in this particular episode are going to be strictly regarding sports genomics, sport performance and enhancing our human performance, not necessarily treating of debilitating and serious diseases. Now, one of the main reasons why I wanted to do this episode is because not only how interesting the field is, but because of how much it's growing and transferring over into the general population. Genetic testing used to be incredibly expensive and therefore basically inaccessible for most people, and that's no longer the case. The first human genome sequence cost around $3 billion for one person, and now there are thousands of different companies that offer these testing for anywhere between a couple of hundred dollars to up to a thousand. In addition to that, our knowledge is expanding greatly. Just in February of 2024, one of the major projects here in the US called the All of Us Project, which I'll discuss a little bit later, just announced the discovery of 275 million new genetic variants in humans. And so we're learning more and more every day. And by that, I mean a lot and lot more every single day. And because of all these things, people are really interested and excited. And in fact, there was a study that suggested up to 10% of athletes have already had some sort of genetic testing done. In addition, many of you have also probably had it done already, you thought about it, or you've had clients, patients, athletes, or friends of yours ask you about it. And so because of that, I really wanted to get into what do we currently know about the science of sports genomics. And while I'm always a proponent of you learning more about your body, we need to approach this field carefully because it is so new. And there are some potential consequences many folks don't realize. For example, there are data initially showing that people will take nutrition and exercise advice that is based on their genetics more seriously than when based on other factors. Now, this can be good or bad. Obviously, the positive here is if that helps you drive adherence. We know this is one of the number one problems or limitations with successful nutrition or exercise interventions, people being consistent and sticking to their program. So if this can help with that, that is fantastic. However, it can lead to feelings of hopelessness, if you will. So if your genetic report came back and told you that you're not going to respond well to exercise, that you can't eat a particular food type, or your body doesn't do something well, you can hopefully see how that can be really harmful to some people. It can kill motivation, it can make them feel like they're never going to get better, or any number of things. And I don't want to put emotions and thoughts into people's heads, but you can understand how this could be really, really detrimental. And so it's important for me to help you understand what this data really means, how to properly interpret it, how to properly contextualize it, so that you can use it for your advantage, or at least try to minimize the potential downsides. For example, some data actually suggests that the impact of your belief in your genetics outpaces the actual impact of the genetics themselves. For example here, if you had a particular genetic profile that improved muscle growth by 5% in response to exercise, well, your actual belief that you have the genetics for that might make you grow more so, that 5%, than the actual explanation of the genetics themselves. And so if you were to get testing done, recommend it, or know of somebody that had some genetic testing done, their belief in what they think is gonna happen, positively or negatively, is really, really impactful. And we know this objectively in peer-reviewed published research. And so again, this is why I think it's important that we really get a better understanding of what is genetic testing for performance? What does it really mean? What do we know about the data? How seriously should I take it? What can we use it for? What shouldn't we use it for? And what is maybe more in the middle that will leave up to you for interpretation? Now before we go too much further, I'd like to take a quick break and thank our sponsors because they make this show possible. Not only are they on this list because they offer great products and services, but because I actually personally love them and use them myself. Today's episode is brought to you by AG1. AG1 is a foundational nutrition greens supplement. What's that mean? It means that AG1 provides a comprehensive variety of vitamins, minerals, probiotics, and adaptogens in an easy to drink greens powder. Getting your nutritional right is hard for many people. I certainly know that I have clients who really struggle, for whatever reason, to get the proper nutrients from whole food sources. Now, AG1 is not a replacement for eating high quality whole foods, but it is a great foundational supplement for filling in the gaps where needed. I've also personally found that with many of my clients, AG1 helps move them just in the right direction for eating more high quality foods because it helps them with cravings, digestion and many other benefits. I especially personally like taking AG1 when I'm on vacation or traveling because it helps me just sort of stay on track with my nutrition. I know that missing a few days of getting the proper vitamins and minerals and other micronutrients is not a big deal at all. That's not really how those things work. But for me, again, I just like knowing that I'm kind of staying somewhat on track when I'm definitely not making the best nutrition and food choices of my life. If you'd like to try AG1, you can go to drinkag1.com/perform to receive five free travel packs plus a year supply of vitamin D3 plus K2. Again, that's drinkag1.com/perform to receive five free travel packs plus a year supply of vitamin D3 plus K2. Today's episode is also brought to you by Rhone. Rhone is a premium active wear company that is easily my favorite in the world. Few things have aggravated my wife more than my clothing choices. Let's be honest, fashion is not exactly my strong suit. Partially because I have just no sense of style, but also because I'm neurotic about texture and feel. There's not a single brand I've tried over the years that has the same quality, feel and fit that Rhone has absolutely mastered. Rhone uses best in class materials to allow their products to be lightweight and breathable, but still durable enough to last even when you're training super hard. I remember the first time my wife wore it for a cycling workout, and she, who let's just say is well-versed in the active wear world, was genuinely surprised by how soft and stretchy but supportive the material was. The Rhone women's collection actually just launched and is already filled with great reviews online. The Rhone base training shorts are brilliant as well. They fit perfectly and have the right amount of stretch to allow total freedom of movement. They also have pockets, which I like, and zippered pockets that are sneaky helpful for holding hotel keys and things like that. The Atmosphere tee and commuter business shirts completely blew my mind. I do not understand how they made this material. I'll never go back. Trust me here, friends, just stunning craftsmanship all the way around. If you'd like to try Rhone, go to Rhone spelled rhone.com/perform to get 25% off your first order. Again, that's rhone.com/perform to get 25% off your first order. Let's get started by talking about what sports genomics actually is. At the very highest level, your genome is not the same as your genes or your genotype. What's the difference here? All right. Your genome is the entire collection of genetic material that is transmitted from a parent to an offspring. So everything you got from mom and dad altogether is your genome. Now, that genome is a big long strain of DNA. Your DNA is made up of actually basically four different things that are called base pairs. You may remember this from middle school or high school science class. You've got the A, T, C and G. It doesn't even matter at this point if you know what those stand for. But you have all these base pairs. So in total, you've got about 3.2 billion base pairs. So 3.2 billion Cs, T's, A's and G's all stringed together. So you put those all together and that becomes your DNA. All your DNA combined is known as your genome. A gene is actually just a specific portion of those DNA strands that encodes or makes a biologically active element, mostly RNA, that then turns into a protein. Another way to think about this is you have a bunch of genes in your DNA. Those genes are a certain number of base pairs, typically about 1,500 long, plus or minus. So for every 1,500 base pairs, you've got a gene. That gene then makes an RNA. That RNA then makes a protein. And so your genome is a collection of all your genes, and all the proteins you make of that is called your proteome. Now that word is important. We're going to come back to that later. Genes control all the different proteins you make, but that's just potential. Just because you have a gene, it just means you have the ability to make a particular protein. It doesn't mean you're actually going to. So it's just the potential for a protein, not actual result in protein. One of the most important things we have to realize at this point is that all of us, all humans, have the exact same genes. In fact, this is when you've heard things like, humans are 99.9% identical to chimpanzees at the genetic level or something like that. That's what they mean. We have almost the exact same set of genes. What makes us unique in individuals is the fact that within each individual gene, we have slight variations. Okay, now these variations is like 0.1%, and so most of humans are 99.9% the same, but that 0.1% has such a big magnitude when amplified into your actual protein and proteome, that it creates the uniqueness that is all 8 billion of us. And so really the thing that makes us special here, and a point I'm going to drive to a lot is, it's not the genes per se that make us unique and special and different. It's how those are actually transmitted into resulting proteins that allow us to be these unique human beings and to never have the same one of us twice. A perfect example of this is our friend from earlier, Aero Montorranta. Now, Aero actually had a really specific mutation where he actually had a G to A transition, so he had a G base pair instead of an A, at base pairs 6000 and two, okay? Now, that was actually particularly significant for him. That actually caused a special thing to happen here, which is what's called a TGG, so a three base pair segment that was supposed to code for amino acid called tryptophan. You may recognize that thing. That's the amino acids in Turkey that makes you all sleepy. So you're supposed to code for that, but that little mutation, that single base pair switch out actually caused that instead of making the tryptophan to make what's called a stop codon, just tells the gene to stop replicating if you want to think about it like that. Now, that result means that when he created his EPO receptor, that receptor actually then became 70 amino acids shorter than normal and made it hyperactive. So to recap, he had the exact same gene. He had the EPO gene that all of us share, but his had one base pair switch out. And so one base pair switch out had a huge impact on the resulting protein, which had that a huge impact on his overall body because it was much more receptive to the EPO-R. And so this is why, again, when they tested him, his EPO concentrations were normal. And in fact, this is one of the main things that led to WADA, the World Anti-Doping Association, generating and creating a program called the Athlete Passport, because they started to recognize that we can't just test for levels. And you see, prior to this, if someone just had a high hematocrit level, they would either not be allowed to race or they would be flagged and banned because they assumed they were cheating. Eventually, WADA had to recognize, there are some people who are just different. And this is normal for them. They're not cheating. And so the passport idea says, we'll just track you over time. And if you jump way up or down in some biological metric, then we may have some indication that you're cheating. But back to our point here. So everyone has the same genes, but some of us have these small variations in any individual or given gene that has a big impact on the amount of proteins we make, which has a huge impact on who you are as a human being. But we gotta go one layer deeper, because in fact, you actually have two copies of every gene. Now we call these alleles. One copy comes from mom, one copy comes from dad. So if we go back to our EPO receptor, it would actually function more like this. Let's say a normal EPO receptor is N for normal. And so what we would say is that EPO gene would be EPO-R-N for normal. And let's say the endurance one that Aero got, we'll call it E for endurance. So you could either have EPO-R-N or EPO-R-E. But since you're getting one of each copy, you could be what we call homozygous, which would be EPO-R-N-N.