Identification of Genomic Predictors of Muscle Fiber Size.

The greater muscle fiber cross-sectional area (CSA) is associated with greater skeletal muscle mass and strength, whereas muscle fiber atrophy is considered a major feature of sarcopenia. Muscle fiber size is a polygenic trait influenced by both environmental and genetic factors. However, the genetic variants underlying inter-individual differences in muscle fiber size remain largely unknown. The aim of our study was to determine whether 1535 genetic variants previously identified in a genome-wide association study of appendicular lean mass are associated with the CSA of fast-twitch muscle fibers (which better predict muscle strength) in the m. vastus lateralis of 148 physically active individuals (19 power-trained and 28 endurance-trained females, age 28.0 ± 1.1; 28 power-trained and 73 endurance-trained males, age 31.1 ± 0.8). Fifty-seven single-nucleotide polymorphisms (SNPs) were identified as having an association with muscle fiber size (p < 0.05). Of these 57 SNPs, 31 variants were also associated with handgrip strength in the UK Biobank cohort (n = 359,729). Furthermore, using East Asian and East European athletic (n = 731) and non-athletic (n = 515) cohorts, we identified 16 SNPs associated with athlete statuses (sprinter, wrestler, strength, and speed-strength athlete) and weightlifting performance. All SNPs had the same direction of association, i.e., the lean mass-increasing allele was positively associated with the CSA of muscle fibers, handgrip strength, weightlifting performance, and power athlete status. In conclusion, we identified 57 genetic variants associated with both appendicular lean mass and fast-twitch muscle fiber size of m. vastus lateralis that may, in part, contribute to a greater predisposition to power sports.

Genomic Predictors of Brisk Walking Are Associated with Elite Sprinter Status.

Brisk walkers are physically more active, taller, have reduced body fat and greater physical fitness and muscle strength. The aim of our study was to determine whether genetic variants associated with increased walking pace were overrepresented in elite sprinters compared to controls. A total of 70 single-nucleotide polymorphisms (SNPs) previously identified in a genome-wide association study (GWAS) of self-reported walking pace in 450,967 European individuals were explored in relation to sprinter status. Genotyping of 137 Russian elite sprinters and 126 controls was performed using microarray technology. Favorable (i.e., high-speed-walking) alleles of 15 SNPs (FHL2 rs55680124 C, SLC39A8 rs13107325 C, E2F3 rs4134943 T, ZNF568 rs1667369 A, GDF5 rs143384 G, PPARG rs2920503 T, AUTS2 rs10452738 A, IGSF3 rs699785 A, CCT3 rs11548200 T, CRTAC1 rs2439823 A, ADAM15 rs11264302 G, C6orf106 rs205262 A, AKAP6 rs12883788 C, CRTC1 rs11881338 A, NRXN3 rs8011870 G) were identified as having positive associations with sprinter status (p < 0.05), of which IGSF3 rs699785 survived correction for multiple testing (p = 0.00004) and was linked (p = 0.042) with increased proportions of fast-twitch muscle fibers of m. vastus lateralis in physically active men (n = 67). Polygenic analysis revealed that individuals with ≥18 favorable alleles of the 15 SNPs have an increased odds ratio of being an elite sprinter when compared to those with ≤17 alleles (OR: 7.89; p < 0.0001). Using UK Biobank data, we also established the association of 14 favorable alleles with low BMI and fat percentage, 8 alleles with increased handgrip strength, and 7 alleles with increased height and fat-free mass. In conclusion, we have identified 15 new genetic markers associated with sprinter status.

Genomic predictors of testosterone levels are associated with muscle fiber size and strength.

PURPOSE: Circulating testosterone levels are a heritable trait with anabolic properties in various tissues, including skeletal muscle. So far, hundreds of single nucleotide polymorphisms (SNPs) associated with testosterone levels have been identified in nonathletic populations. The aim of the present study was to test the association of 822 testosterone-increasing SNPs with muscle-related traits (muscle fiber size, fat-free mass and handgrip strength) and to validate the identified SNPs in independent cohorts of strength and power athletes. METHODS: One hundred and forty-eight physically active individuals (47 females, 101 males) were assessed for cross-sectional area (CSA) of fast-twitch muscle fibers. Significant SNPs were further assessed for fat-free mass and handgrip strength in > 354,000 participants from the UK Biobank cohort. The validation cohorts included Russian elite athletes. RESULTS: From an initial panel of 822 SNPs, we identified five testosterone-increasing alleles (DOCK3 rs77031559 G, ESR1 rs190930099 G, GLIS3 rs34706136 TG, GRAMD1B rs850294 T, TRAIP rs62260729 C) nominally associated (P < 0.05) with CSA of fast-twitch muscle fibers, fat-free mass and handgrip strength. Based on these five SNPs, the number of testosterone-increasing alleles was positively associated with testosterone levels in male athletes (P = 0.048) and greater strength performance in weightlifters (P = 0.017). Moreover, the proportion of participants with ≥ 2 testosterone-increasing alleles was higher in power athletes compared to controls (68.9 vs. 55.6%; P = 0.012). CONCLUSION: Testosterone-related SNPs are associated with muscle fiber size, fat-free mass and strength, which combined can partially contribute to a greater predisposition to strength/power sports.

The BDNF-Increasing Allele is Associated With Increased Proportion of Fast-Twitch Muscle Fibers, Handgrip Strength, and Power Athlete Status.

ABSTRACT: Guilherme, JPLF, Semenova, EA, Borisov, OV, Kostryukova, ES, Vepkhvadze, TF, Lysenko, EA, Andryushchenko, ON, Andryushchenko, LB, Lednev, EM, Larin, AK, Bondareva, EA, Generozov, EV, and Ahmetov, II. The BDNF-increasing allele is associated with increased proportion of fast-twitch muscle fibers, handgrip strength, and power athlete status. J Strength Cond Res 36(7): 1884-1889, 2022-The brain-derived neurotrophic factor (BDNF) is involved in neurogenesis and formation of regenerated myofibers following injury or damage. A recent study suggested that the BDNF overexpression increases the proportion of fast-twitch muscle fibers, while the BDNF deletion promotes a fast-to-slow transition. The purpose of this study was to evaluate the association between the BDNF gene rs10501089 polymorphism (associated with blood BDNF levels), muscle fiber composition, and power athlete status. Muscle fiber composition was determined in 164 physically active individuals (113 men, 51 women). BDNF genotype and allele frequencies were compared between 508 Russian power athletes, 178 endurance athletes, and 190 controls. We found that carriers of the minor A-allele (the BDNF-increasing allele) had significantly higher percentage of fast-twitch muscle fibers than individuals homozygous for the G-allele (males: 64.3 [7.8] vs. 50.3 [15.8]%, p = 0.0015; all subjects: 64.1 ± 7.9 vs. 49.6 ± 14.7%, p = 0.0002). Furthermore, the A-allele was associated (p = 0.036) with greater handgrip strength in a sub-group of physically active subjects (n = 83) and over-represented in power athletes compared with controls (7.7 vs. 2.4%, p = 0.0001). The presence of the A-allele (i.e., AA+AG genotypes) rather than GG genotype increased the odds ratio of being a power athlete compared with controls (odds ratio [OR]: 3.43, p = 0.00071) or endurance athletes (OR: 2.36, p = 0.0081). In conclusion, the rs10501089 A-allele is associated with increased proportion of fast-twitch muscle fibers and greater handgrip strength, and these may explain, in part, the association between the AA/AG genotypes and power athlete status.

The MCT1 gene Glu490Asp polymorphism (rs1049434) is associated with endurance athlete status, lower blood lactate accumulation and higher maximum oxygen uptake.

The purpose of this study was to explore the association of the MCT1 gene Glu490Asp polymorphism (rs1049434) with athletic status and performance of endurance athletes. A total of 1,208 Brazilians (318 endurance athletes and 890 non-athletes) and 867 Europeans (315 endurance athletes and 552 non-athletes) were evaluated in a case-control approach. Brazilian participants were classified based on self-declared ethnicity to test whether the polymorphism was different between Caucasians and Afro-descendants. Moreover, 66 Hungarian athletes underwent an incremental test until exhaustion to assess blood lactate levels, while 46 Russian athletes had their maximum oxygen uptake ( V ⋅ O 2 max ) compared between genotypes. In the Brazilian cohort, the major T-allele was more frequent in Caucasian top-level competitors compared to their counterparts of lower competitive level (P = 0.039), and in Afro-descendant athletes compared to non-athletes (P = 0.015). Similarly, the T-allele was more frequent in European athletes (P = 0.029). Meta-analysis of the Brazilian and European cohorts confirmed that the T-allele is over-represented in endurance athletes (OR: 1.48, P = 0.03), especially when Afro-descendant athletes were included in the meta-analysis (OR: 1.58, P = 0.005). Furthermore, carriers of the T/T genotype accumulated less blood lactate in response to intense effort (P < 0.01) and exhibited higher V ⋅ O 2 max (P = 0.04). In conclusion, the Glu490Asp polymorphism was associated with endurance athletic status and performance. Our findings suggest that, although ethnic differences may exist, the presence of the major T-allele (i.e., the Glu-490 allele) favours endurance performance more than the mutant A-allele (i.e., the 490-Asp allele).

Are Genome-Wide Association Study Identified Single-Nucleotide Polymorphisms Associated With Sprint Athletic Status? A Replication Study With 3 Different Cohorts.

PURPOSE: To replicate previous genome-wide association study identified sprint-related polymorphisms in 3 different cohorts of top-level sprinters and to further validate the obtained results in functional studies. METHODS: A total of 240 Japanese, 290 Russians, and 593 Brazilians were evaluated in a case-control approach. Of these, 267 were top-level sprint/power athletes. In addition, the relationship between selected polymorphisms and muscle fiber composition was evaluated in 203 Japanese and 287 Finnish individuals. RESULTS: The G allele of the rs3213537 polymorphism was overrepresented in Japanese (odds ratio [OR]: 2.07, P = .024) and Russian (OR: 1.93, P = .027) sprinters compared with endurance athletes and was associated with an increased proportion of fast-twitch muscle fibers in Japanese (P = .02) and Finnish (P = .041) individuals. A meta-analysis of the data from 4 athlete cohorts confirmed that the presence of the G/G genotype rather than the G/A+A/A genotypes increased the OR of being a sprinter compared with controls (OR: 1.49, P = .01), endurance athletes (OR: 1.79, P = .001), or controls + endurance athletes (OR: 1.58, P = .002). Furthermore, male sprinters with the G/G genotype were found to have significantly faster personal times in the 100-m dash than those with G/A+A/A genotypes (10.50 [0.26] vs 10.76 [0.31], P = .014). CONCLUSION: The rs3213537 polymorphism found in the CPNE5 gene was identified as a highly replicable variant associated with sprinting ability and the increased proportion of fast-twitch muscle fibers, in which the homozygous genotype for the major allele (ie, the G/G genotype) is preferable for performance.

The A-allele of the FTO Gene rs9939609 Polymorphism Is Associated With Decreased Proportion of Slow Oxidative Muscle Fibers and Over-represented in Heavier Athletes.

Guilherme, JPLF, Egorova, ES, Semenova, EA, Kostryukova, ES, Kulemin, NA, Borisov, OV, Khabibova, SA, Larin, AK, Ospanova, EA, Pavlenko, AV, Lyubaeva, EV, Popov, DV, Lysenko, EA, Vepkhvadze, TF, Lednev, EM, Govorun, VM, Generozov, EV, Ahmetov, II, and Lancha Junior, AH. The A-allele of the FTO gene rs9939609 polymorphism is associated with decreased proportion of slow oxidative muscle fibers and over-represented in heavier athletes. J Strength Cond Res 33(3): 691-700, 2019-The purpose of this study was to explore the frequency of the FTO T > A (rs9939609) polymorphism in elite athletes from 2 cohorts (Brazil and Russia), as well as to find a relationship between FTO genotypes and muscle fiber composition. A total of 677 athletes and 652 nonathletes were evaluated in the Brazilian cohort, whereas a total of 920 athletes and 754 nonathletes were evaluated in the Russian cohort. It was found a trend for a lower frequency of A/A genotype in long-distance athletes compared with nonathletes (odds ratio [OR]: 0.65; p = 0.054). By contrast, it was found an increased frequency of the A-allele in Russian power athletes. The presence of the T/A + A/A genotypes rather than T/T increased the OR of being a Russian power athlete compared with matched nonathletes (OR: 1.45; p = 0.002). Different from that observed in combat sports athletes of lighter weight categories, the A-allele was also over-represented in combat sports athletes of heavier weight categories. The presence of the T/A + A/A genotypes rather than T/T increased the OR of being a combat sports athlete of heavier weight categories compared with nonathletes (OR: 1.79; p = 0.018). Regarding the muscle fibers, we found that carriers of the A/A genotype had less slow-twitch muscle fibers than T-allele carriers (p = 0.029). In conclusion, the A/A genotype of the FTO T > A polymorphism is under-represented in athletes more reliant on a lean phenotype and associated with decreased proportion of slow-twitch muscle fibers, while is over-represented in strength and heavier athletes.