Decoding the genetics of marathon runners
Dr Haran Sivapalan
September 26, 2018
Eliud Kipchoge recently demolished the world marathon record, wiping an astonishing 1 minute 18 seconds off the previous record time. The 33-year-old Kenyan athlete covered the Berlin Marathon course in a total of 2 hours 1 minute and 39 seconds: that’s an average pace of 4 min: 38 s per mile, sustained over 26.2 consecutive miles (or 42 km)!
To put that figure in perspective, when the FitnessGenes staff team ran a 4 x 5 km relay in July, we had an average pace of 6 min: 24 s per mile. And, that’s with four separate runners!
Of course, it makes little sense to compare our pedestrian performance to that of an elite athlete. Elite marathon times are primarily the result of demanding, high-volume training regimes, exacting diets, and top coaching. But, there are also other non-training related factors to consider.
Firstly, psychological traits are important. Kipchoge is famed for his mental strength, determination and self-discipline, and the author of the sagacious: “Only the disciplined ones are free in life. If you are undisciplined, you are a slave to your moods. You are a slave to your passions.”
Secondly, and without meaning to diminish any of the above factors, Kipchoge also likely benefits from abundant natural talent: that seemingly innate, raw ability that separates elite athletes from mere mortals. More precisely, he and other elite marathon runners may have an advantageous combination of genes that better suit them to the demands of long-distance running.
Nature versus nurture
In his seminal book, The Sports Gene, writer David Epstein contends that genetics play more of a role in elite athletic performance than we as a society like to admit. For example, we know that carrying the R allele of the ACTN3 gene confers a significant advantage in power-related sports.
Virtually every Olympic sprinter tested to date has at least one copy of the R allele. Delving deeper, biopsies of muscle show us that the R allele allows individuals to produce the protein alpha-actinin-3, a component of fast-twitch muscle fibers used in explosive, high-velocity muscle contractions - precisely what’s needed in sprinting.
So, some genes may be helpful in short-distance, short-duration sprinting that is dependent mainly on anaerobic respiration for energy. But what about the other end of the running spectrum? Are there genes that can help someone use their slow-twitch muscle fibers, aerobic respiration pathways and cardiovascular endurance to propel them over 26.2 miles?
One study examined 438 athletes who ran the 2007 and 2008 Olympus Marathon in Greece, a grueling course that involves over 2 km of elevation gain. Rather than look at the whole genome, the researchers focussed on variants of 8 genes related to carbohydrate and fat metabolism, muscle contraction and heart and lung function. If certain gene variants were either overrepresented in these athletes compared to the general population or significantly associated with quicker finish times, then this would tentatively suggest that such genes confer an advantage for marathon running.
In agreement with a previous study on Ironman triathletes, the researchers found that the TT genotype of the BDKRB2 gene was strongly associated with marathon performance. The BDKRB2 gene encodes a receptor for bradykinin, a molecule that causes blood vessels to dilate and helps to regulate blood pressure. Individuals with the T allele have been demonstrated to have higher levels of the bradykinin receptor.
While more research is needed, it’s possible that this gene variant facilitates greater blood flow to exercising muscles, allowing them to use oxygen and nutrients more effectively: exactly what’s needed in long-distance running.
Another gene that may also help marathon runners supply their muscles with oxygenated, nutrient-rich blood is the ADRB2 gene. This gene encodes the beta-2 adrenergic receptor, a protein to which adrenaline binds, thereby orchestrating our fight-or-flight response. When the beta-2 receptor is stimulated, our lung airways expand, our heart rate increases, our blood vessels dilate, and we begin to burn more fat for energy. All of these physiological changes allow us to run.
According to an analysis of the Mount Olympus athletes, one variant (the A allele) of the ADRB2 gene was associated with faster marathon times. It’s possible that this variant helps the cardiovascular system to pump blood to exercising muscles more effectively. Additionally, it may also promote favorable changes in muscle metabolism, allowing muscles to recycle more lactate as energy. Both of these changes are helpful for long-duration exercise.
Although the study of Olympus runners didn’t find a significant association, other studies have linked a variant of the PGC1A (also known as the PPARGC1A) gene to improved endurance performance. The PGC1A gene encodes an important protein called PGC-1α, which, in part, causes metabolic changes within skeletal muscle in response to aerobic exercise. One of these changes is an increased number of mitochondria, the parts of the cell responsible for aerobic respiration and generating energy. Marathon runners clearly stand to benefit from muscle cells that can churn out energy over long periods of time.
On this note, one analysis of elite Spanish long-distance runners found that the G allele of the PGC1A gene was more common than other variants. Given that the G allele is linked to a higher amount of PGC-1 α protein, this may suggest that this gene variant gives rise to muscles that are more responsive to aerobic exercise.
Training still matters!
It’s important to understand that possessing any of the above gene variants doesn’t mean you’ll start running 2-hour marathons. Firstly, training is obviously a critical factor. The most significant difference between an amateur and elite marathon runner is likely to be the hours spent training: running around a track, in a gym or doing long runs.
Secondly, elite athletic performance is influenced by hundreds of genes, all acting in concert with one another and with the environment. Generally speaking, a few gene variants in isolation are unlikely to have a significant effect on athletic performance.
The physiological factors imperative to running performance such as VO2 max (how efficiently you can deliver oxygen to working muscles) and running economy (how efficiently you use oxygen to run at a given speed), are all influenced by genes, training, diet, as well as the mental strength to push yourself to the limit.