Humans vary in their ability to achieve success in sports, and this variability mostly depends on genetic factors. The main goal of this work was to review the current progress in the understanding of genetic determinism of athlete status and to describe some novel and important DNA polymorphisms that may underlie differences in the potential to be an elite athlete. In the past 19 years, at least 155 genetic markers (located within almost all chromosomes and mtDNA) were found to be linked to elite athlete status (93 endurance-related genetic markers and 62 power/strength-related genetic markers). Importantly, 41 markers were identified within the last 2 years by performing genome-wide association studies (GWASs) of African-American, Jamaican, Japanese, and Russian athletes, indicating that GWASs represent a promising and productive way to study sports-related phenotypes. Of note, 31 genetic markers have shown positive associations with athlete status in at least 2 studies and 12 of them in 3 or more studies. Conversely, the significance of 29 markers was not replicated in at least 1 study, raising the possibility that several findings might be false-positive. Future research, including multicentre GWASs and whole-genome sequencing in large cohorts of athletes with further validation and replication, will substantially contribute to the discovery of large numbers of the causal genetic variants (mutations and DNA polymorphisms) that would partly explain the heritability of athlete status and related phenotypes.

The performance of professional strength and power athletes is influenced, at least partly, by genetic components. The main aim of this study was to investigate individually and in combination the association of ACE (I/D), ACTN3 (R577X) and PPARGC1A (Gly482Ser) gene polymorphisms with strength/power-oriented athletes’ status in two cohorts of European athletes. A cohort of European Caucasians from Russia and Lithuania (161 athletes: by groups – weightlifters (87), powerlifters (60), throwers (14); by elite status – ‘elite’ (104), ‘sub-elite’ (57); and 1,202 controls) were genotyped for ACE, ACTN3 and PPARGC1A polymorphisms. Genotyping was performed by polymerase chain reaction and/or restriction fragment length polymorphism analysis. Statistically significant differences in ACTN3 (R577X) allele/genotype distribution were not observed in the whole cohort of athletes or between analysed groups separately when compared with controls. The odds ratio for athletes compared to controls of the ACE I/I genotype was 1.71 (95% CI 1.01-2.92) in the Russian cohort and for the ACE I/D genotype it was 2.35 (95% CI 1.10-5.06) in the Lithuanian cohort. The odds ratio of being a powerlifter in PPARGC1A Ser/Ser genotype carriers was 2.11 (95% CI: 1.09-4.09, P = 0.026). The ACTN3 (R577X) polymorphism is not associated with strength/power athletic status in two cohorts of European athletes. The ACE I/I genotype is probably the ‘preferable genotype’ for Russian athletes and the ACE I/D genotype for Lithuanian strength/power athletes. We found that the PPARGC1A (Gly482Ser) polymorphism is associated with strength/power athlete status. Specifically, the PPARGC1A Ser/Ser genotype is more favourable for powerlifters compared to controls.

The substantial decline in skeletal muscle mass, strength, and gait speed is a sign of severe sarcopenia, which may partly depend on genetic risk factors. So far, hundreds of genome-wide significant single nucleotide polymorphisms (SNPs) associated with handgrip strength, lean mass and walking pace have been identified in the UK Biobank cohort; however, their pleiotropic effects on all three phenotypes have not been investigated. By combining summary statistics of genome-wide association studies (GWAS) of handgrip strength, lean mass and walking pace, we have identified 78 independent SNPs (from 73 loci) associated with all three traits with consistent effect directions. Of the 78 SNPs, 55 polymorphisms were also associated with body fat percentage and 25 polymorphisms with type 2 diabetes (T2D), indicating that sarcopenia, obesity and T2D share many common risk alleles. Follow-up bioinformatic analysis revealed that sarcopenia risk alleles were associated with tiredness, falls in the last year, neuroticism, alcohol intake frequency, smoking, time spent watching television, higher salt, white bread, and processed meat intake; whereas protective alleles were positively associated with bone mineral density, serum testosterone, IGF1, and 25-hydroxyvitamin D levels, height, intelligence, cognitive performance, educational attainment, income, physical activity, ground coffee drinking and healthier diet (muesli, cereal, wholemeal or wholegrain bread, potassium, magnesium, cheese, oily fish, protein, water, fruit, and vegetable intake). Furthermore, the literature data suggest that single-bout resistance exercise may induce significant changes in the expression of 26 of the 73 implicated genes in m. vastus lateralis, which may partly explain beneficial effects of strength training in the prevention and treatment of sarcopenia. In conclusion, we have identified and characterized 78 SNPs associated with sarcopenia and 55 SNPs with sarcopenic obesity in European-ancestry individuals from the UK Biobank.

We aimed to replicate, in a specific athletic event cohort (only track and field) and in two different ethnicities (Japanese and East European, i.e. Russian and Polish), original findings showing the association of the angiotensin-II receptor type-2 gene (AGTR2) rs11091046 A>C polymorphism with athlete status. We compared genotypic frequencies of the AGTR2 rs11091046 polymorphism among 282 track and field sprint/power athletes (200 men and 82 women), including several national record holders and Olympic medallists (214 Japanese, 68 Russian and Polish), and 2024 control subjects (842 men and 1182 women) (804 Japanese, 1220 Russian and Polish). In men, a meta-analysis from the two combined cohorts showed a significantly higher frequency of the C allele in athletes than in controls (odds ratio: 1.62, P=0.008, heterogeneity index I2=0%). With regard to respective cohorts, C allele frequency was higher in Japanese male athletes than in controls (67.7% vs. 55.9%, P=0.022), but not in Russian/Polish male athletes (61.9% vs. 51.0%, P=0.172). In women, no significant results were obtained by meta-analysis for the two cohorts combination (P=0.850). The AC genotype frequency was significantly higher in Russian/Polish women athletes than in controls (69.2% vs. 42.1%, P=0.022), but not in Japanese women athletes (P=0.226). Our results, in contrast to previous findings, suggested by meta-analysis that the C allele of the AGTR2 rs11091046 polymorphism is associated with sprint/power track and field athlete status in men, but not in women.

The kidney and brain expressed protein (KIBRA) plays an important role in synaptic plasticity. Carriers of the T allele of the KIBRA (WWC1) gene rs17070145 C/T polymorphism have been reported to have enhanced spatial ability and to outperform individuals with the CC genotype in working memory tasks. Since ability in chess and science is directly related to spatial ability and working memory, we hypothesized that the KIBRA T allele would be positively associated with chess player status and PhD status in science. We tested this hypothesis in a study involving 2479 individuals (194 chess players, 119 PhD degree holders in STEM fields, and 2166 controls; 1417 males and 1062 females) from three ethnicities (236 Kazakhs, 1583 Russians, 660 Tatars). We found that frequencies of the T allele were significantly higher in Kazakh (66.9 vs. 55.1%; p = 0.024), Russian (44.8 vs. 32.0%; p = 0.0027), and Tatar (51.5 vs. 41.8%; p = 0.035) chess players compared with ethnically matched controls (meta-analysis for CT/TT vs. CC: OR = 2.05, p = 0.0001). In addition, none of the international chess grandmasters (ranked among the 80 best chess players in the world) were carriers of the CC genotype (0 vs. 46.3%; OR = 16.4, p = 0.005). Furthermore, Russian and Tatar PhD holders had a significantly higher frequency of CT/TT genotypes compared with controls (meta-analysis: OR = 1.71, p = 0.009). Overall, this is the first study to provide comprehensive evidence that the rs17070145 C/T polymorphism of the KIBRA gene may be associated with ability in chess and science, with the T allele exerting a beneficial effect.