The current meta-analysis investigated the potential association between specific genomic variants and athletic performance. This study represents the most extensive meta-analysis conducted thus far to explore this pertinent issue, which holds significance not only within the realm of research but also from an ethical standpoint. Contrary to the few other systematic reviews and meta-analyses in the literature that only focused on the ACE and the ACTN3 genes [5, 11], this study aimed to identify correlations between genetic loci and athletic performance in an agnostic fashion, resulting in a much bigger number of genes that were reported to be associated with athletic performance. However, the small number of studies in the majority of genes (Table 1) did not allow us to perform a meta-analysis for all these genes that would be properly powered, in statistical terms, restricting us only to the ACE and ACTN3 genes (see also below).

The identification of sports talent is based both on physical and physiological characteristics and the overall performance of athletes in a specific sports discipline. Contemporary studies attempted to correlate genetic loci with athletic performance. Consequently, many genetic testing laboratories offer these services and promise to revolutionize the field of sports. These tests try, through the detection of specific genomic variants, to elucidate the athletic performance potential of individuals, especially the youth. The goal is to contribute to the choice of the appropriate sports career and enable personalized training. Such programs promise to maximize the range of capabilities and minimize the risk of injury.

Herein, from 4228 articles, only 107 (2.53%) were eligible for inclusion in our study, which touched upon 37 different genes and 55 variants (Table 1). From the 37 different genes, for only 2 (5.41%) genes and only for 2 variants, there were enough articles to allow for a proper meta-analysis. Notably, for 27 genomic variants in 22 genes (52.6% of the total number of genes included in our study), there was only a single study that addressed their association with sports performance, while one of these genes, namely the high Fe gene (HFE) with the p.C282Y and p.H63D variants, is mostly associated with hemochromatosis (a PubMed search performed in April 2024 with the keywords “HFE” and “Hemochromatosis” revealed 3,174 results). Our data show that only the ACE Alu I/D and ACTN3 p.R577X variants, studied by 29 and 37 articles each, have been adequately studied for their association with elite athletic performance. The next most well-studied variants were the rs4253778 and rs8192678 variants in the Peroxisome proliferator-activated receptor alpha (PPARA) and the PARG Coactivator 1 Alpha (PPARGC1A) gene, respectively, studied by 9 articles each, that were still not eligible for a proper meta-analysis, and the remaining variants were analyzed in less than 6 studies. Furthermore, the studies mentioned above are characterized by the ambiguity of their outcomes, demonstrating a spectrum of associations between the investigated genetic variant and athletic performance. These associations range from a positive to a weak correlation and, in some instances, no discernible correlation at all.

The complexity of confirming a correlation between a genetic variant and sports performance is further compounded by the heterogeneity in sports discipline and the subjective classification of athletes. In other words, the criteria to assign an athlete to the power or endurance category, according to the skills required by their sport of occupation, are not uniform, as shown in Table 3. The table indicates the sports that fall under the banner of endurance or power sports and their performance level, as defined by each study. Gender and/or nationality were not taken into account. Our data show that despite our careful selection of endurance or power athletes deducted from each article, it is evident that they all come from a variety of different sports. Thus, rowing, cross-country skiing, cross-country skating, polo, handball, duathlon, triathlon, pentathlon, running, swimming, and cycling of medium and long distances were characterized as endurance sports. Conversely, wrestling, boxing, judo, bodybuilding, powerlifting, weightlifting, javelin, high jump, long jump, triple jump, football, kayak, volleyball, ice hockey, and running were characterized as power sports. We opted to follow the athlete and sport classification reported in each of the study included in our meta-analysis and neither to reclassify the athletes’ groups nor to redetermine the type of sport, as this would introduce bias in our analysis. We understand of course that determining an athlete’s performance as elite, sub-elite, etc., cannot be objectively determined, and credible criteria for such classification are currently not established. This is a major limitation of these studies attempting to correlate genomic variants with athletic performance, not to mention the strong influence of epigenetics as well as environmental factors in determining the overall outcome of a world-class competition.

It becomes apparent that the delineation between endurance and power athletes is determined on a study-by-study basis. For example, some studies considered runners up to 400 m as power athletes, while other studies limit this categorization to 100 m sprinters. Moreover, in team sports such as football, not all players can be considered of the same skill, as players’ skills depend on their position in the field, which demands different qualities. Druzhevskaya and coworkers [3] attempted to comprehensively categorize athletes' skills by sport. They revealed that “endurance” skills are also required in sports that belong to the “power” category. Similarly, the definition of the level of athletes differs between studies. However, there is more homogeneity in this classification since many authors comply with the categorization in terms of level, as defined by Druzhevskaya and coworkers [3] and this was the reason to select this classification for the purpose of this meta-analysis.

Upon analyzing the quality of the associations between genes and athletic performance as reported in case–control studies, our meta-analysis revealed inconsistencies in the findings related to ACE Alu I/D and ACTN3 p.R577X variants. It was noted that a positive correlation was found in a relatively small studies with well-defined groups of athletes, while a negative correlation was found in larger studies with a more diverse athletes’ population. This fact, coupled with the varied methodology pursued in each study, and confounders such as the sample size, the inclusion of different sports leading to phenotypic heterogeneity, and ethnic diversity makes it exceedingly challenging to draw firm conclusions regarding the association of these two variants with elite sport performance. For example, considering the aspect of ethnicity, Kenya is known to be home to some of the best runners in the world. If a genomic variant is found to be correlated with endurance in Kenyan runners, it is imperative to confirm the same association in runners of different ethnic backgrounds.

Several sports teams consider the results of these genetic tests seriously when making direct coaching recommendations, as indicated in the literature [2, 9, 14]. While genome-wide association studies (GWAS) have identified possible associations between genes and athletic performance at the study population level, the possible association of each variant at an individual’s level is less consistent. Genetic testing alone cannot conclusively confirm or rule out an individual’s athletic performance [1].

On the other hand, implementing genetic testing for sports performance carries significant ethical considerations. For instance, children who aspire to become world-class athletes can have several negative effects, such as depression and psychological problems, if the genotype supposedly associated with their preferred sport is not detected. Conversely, the results may falsely reassure them that they will become top athletes. Considering these concerns, the governance of sports genomics should be stringently regulated by ethics review committees, aligning with the principles outlined in the Declaration of Helsinki (World Medical Association, 2008), while any genome-guided recommendations for athletic performance should abide to regulatory approval and not simply interpretation of the findings which could be subjective. Moreover, general public access to such tests should be revised considerably. As such, it would be reasonable for all reported genetic associations to remain in the investigational sphere before being allowed to be released to the market until two critical conditions are met: (a) there is a biologically plausible and well-supported molecular mechanism by which the variant could impact athletic performance and (b) replication of the positive association between the variant and athletic performance in several independent studies in different populations. This is essential to mitigate the risk of false positive results that would mislead the interested individuals.

Overall, genomic markers cannot per se predict athletic performance for talent identification due to the multifaceted nature of athletic performance, which is influenced not only by our genetic background but also, and significantly, by various environmental factors. Regarding the genetic background, it is critical to determine other variants associated with resistance to injuries or the ability to recover from them. Furthermore, it is important to consider the association of these variants with pathogens, as has been found for the ACE gene. On the other hand, the difficulty in predicting, let alone simulating, the interplay of environmental factors with one’s genetic profile to contribute to one's final sports performance is unquestionable.

The data from the present study underline that sports genetics is a promising discipline that warrants additional research that includes larger and more homogeneous and well-defined athlete groups from several ethnicities. Without definitive data, the commercial availability of genetic testing for athletic performance to the general public poses significant ethical and safety concerns. Therefore, stringent regulatory oversight by health and legislative bodies is imperative to safeguard the general public against premature application of such genetic testing services.