1. Born Equal: Can genetics make the perfect athlete?

Introduction

Thanks to the dawn of accessible science to map the human genome and the research that is poured into it, genetics are playing a larger role in elite sports. Genetics have a large influence over many attributes necessary for athletic excellence such as strength, muscle size, muscle fibre composition, anaerobic threshold, lung capacity, and flexibility^[1]. The variances (known as genotypes) in these genes affect how these genes work and therefore their physiological input. Whilst nurturing talent is of the utmost importance, we considered how much importance genotypes play in an athlete being attracted to a certain sport and how much influence they can bring to performance. This is a preliminary study analysing specific genotypes known to have influence over athletic traits.

Aim

The aim of the study was to analyse a large database of athletes, comparing their chosen sports and the level that they play. Analysis of the individuals will include genotypes in six heavily studied genes^[2] attributed to athlete potential: ACTN3, MSTN, NOS3, ACE, AMPD1 and TRHR. These results will be collated to see if there are potential correlations between certain genotypes, the sport played, and the levels played. 

Methods

The subject’s data is anonymously pulled from the Muhdo health ltd. database and includes individuals who have chosen that they are athletes through an in-app questionnaire, the term athlete also includes those that use the gym on a regular basis. There are 4447 individuals in the database currently under the status of being an athlete. 1876 female stated as female and 2601 stated as male, they are of varied heritage and have an age range of 23 - 52 years.

Muhdo Health utilise array technology, which is a custom created array from Illumina, this array analyses 1000 genotypes associated with health, performance, and diet. The genotypes chosen for this analysis are as follows:

Table 1. Genotypes analysed.

Athletes are put into certain groups based on the sports they state they play:

Table 2. Sports associated with individuals.

2. Results

After analysis of the results the following was found: (if 75% or above of individuals were attributed to specific sports this would be stated as “predominate” if there was over 90% this would be stated outright)

Table 3. Results.

From the analysed data there are some clear genotypes associated with certain sports whilst others are far vaguer. From the above data alone, the following genotypes maybe associated with specific sports:

Table 4.

3. Discussion

ACTN3

ACTN3 and its single nucleotide polymorphism R577X (rs1815739). R577X directly determines the expression of the α-actinin-3 protein that contributes to the construction of the contractile component in power-generating fast twitch fibres of skeletal muscle. A number of association studies have demonstrated that ACTN3 is a strong candidate in the influence of elite athletic performance^[3]. Most studies attributed the C allele to power sports and the T allele to endurance sports^[3]. In this study the C allele was associated with strength and power sports and was also represented higher in the bodybuilder category, however the T allele was not associated directly with endurance or stamina sports and therefore there is no candidate variance of ACTN3 associated with endurance and stamina sports.

MSTN

MSTN is a gene that makes instructions for producing the protein myostatin, a protein that is part of the transforming growth factor beta family (TGFβ). The TGFβ family of proteins control the growth of tissues in the body, myostatin is found nearly exclusively in the skeletal muscles where it is active before and after birth. The protein actually controls skeletal growth by restraining it, preventing muscles becoming excessively large^[4]. Current research that surrounds myostatin is based around its potential treatment in muscle wasting disorders, animals that have mutations in the encoding gene MSTN show greater muscle mass, strength and in some circumstances reduced bodyfat, which can be known as myostatin-related muscle hypertrophy^[5]. The current study shows that the majority of athletes have the common AA variance in rs1805086 and therefore it is unlikely to affect athletic potential for the majority. However those who are heterozygotes are nearly completely associated with strength, power or bodybuilding with a high level of these competing at a high level in their given sports. There was only one individual with the complete mutation within the gene and this individual competes at the highest level in strength-based sports. It can be stated the G allele is associated with strength, power and bodybuilding which would match the current research on myostatin.

NOS3

The NOS3 gene encodes an enzyme which is responsible for the production of the small molecule nitric oxide (NO). NOS3 is predominantly expressed in the endothelial tissue which lines the circulatory system and heart, where it plays a key role in regulation of NO. NO is a vasodilator and aids the cardiovascular system^[6] when produced correctly, and this vasodilation effect is attributed to an increase in sporting performance through increasing oxygen and other nutrients to muscles. This study shows that the C allele is associated with endurance and stamina and the T allele is associated with strength and power.

ACE

ACE encodes the enzyme angiotensin-converting enzyme, this enzyme is able to cleave proteins. It helps regulate blood pressure and balance fluids and salts in the body. The ACE II genotype has been associated with muscle damage and the DD genotype with protective properties^[7], it is hypothesised that muscle damage can lead to greater adaptation. The II genotype is often attributed to athlete status, however in this study the II genotype was primarily associated with strength and power athletes only.

AMPD1

Adenosine monophosphate deaminase 1 (AMPD1) plays a vital role in the purine nucleotide cycle, the gene encodes an enzyme of the same name. The enzyme coverts adenosine monophosphate to inosine monophosphate which frees an ammonia molecule during the process. Mutations that occur within the AMPD1 gene are one of the most common defects detected in the Caucasian population with a likelihood of having the mutations as 1-2%. Several studies indicate that certain variants can cause fatigue, muscle weakness and muscular cramps, however some even with these variants remain asymptomatic^[8].

The disorder caused by mutations is known as adenosine monophosphate deaminase deficiency type 1 (AMPD1 deficiency) or myoadenylate deaminase deficiency (MADD). The most common symptoms of AMPD1 deficiency are:

1. Exercise intolerance – symptoms of fatigue and fast onset weakness on the commencement of exertion or prolonged exertion.
2. Fatigue – general fatigue is poorly understood and may have multiple pathways; however a surplus of adenosine reduces alertness.
3. Muscle cramping – this may be due to an increased lactate.

Based on the genotypes effect on the body we would expect that those with the T allele would suffer from poor exercise performance. However, this study shows no affect on athlete profile and the genotypes in AMPD1. It should be stated that most athletes had the non-mutated genotypes and for power and strength sports especially it could be stated that at least one C allele is beneficial. Only two individuals had TT and both were endurance/stamina athletes. It is probable that the C allele is beneficial for all sports, especially for power and strength sports and all variances are applicable for endurance and stamina sports.

TRHR

Thyrotropin releasing hormone receptor is a gene that is not as well analysed as the other five in the study. Through a chemical cycle within the body the gene may alter the levels of thyroid-stimulating (TSH) in the blood^[9]. The genotype analysed in the study rs16892496 appears to affect lean body mass^[10], with the C allele causing an increase in lean body mass. In the study the C allele is heavily associated with power and strength sports whereas it is not associated with endurance and stamina sports.

4. Conclusion

This is a preliminary study aiming to investigate the database of Muhdo Health ltd. The primary reasoning is the lack of large genetic database studies being conducted largely on the athlete population. The findings in this study show that there may be a genetic blueprint or profile for certain athletes. Many more genotypes need to be analysed in further study to create a larger picture of how they work together to cause advantages for certain sports. A combination of both nurture and nature will always be required to bring the most out of an individual, however it would be naïve to ignore natural gifts. Genotypes may give an advantage to certain individuals but the lines between which genotype bring the most benefits is blurred, certain genotypes such as those found in MSTN are very uncommon but have very high affinity for power sports and bodybuilding. Other genes such as the once hailed “sports gene” ACTN3^[1] have far more varied distribution and no particular athlete appeared to be hampered from any genotype, however the C allele did have affinity towards strength and power. From the six analysed genes in the study both power/strength athletes and bodybuilders had completed genotype affinity, however these genes seem to have less impact on those that compete in endurance/stamina sports. The  ACTN3 C allele, MSTN G allele, NOS3 T allele, ACE II, AMPD1 C allele and TRHR C allele all show affinity towards power, strength and/or bodybuilding athletes, only the NOS3 C allele showed a true affinity towards endurance/stamina sports.