Genome-Wide Association Study Reveals a Novel Association Between MYBPC3 Gene Polymorphism, Endurance Athlete Status, Aerobic Capacity and Steroid Metabolism.

The genetic predisposition to elite athletic performance has been a controversial subject due to the underpowered studies and the small effect size of identified genetic variants. The aims of this study were to investigate the association of common single-nucleotide polymorphisms (SNPs) with endurance athlete status in a large cohort of elite European athletes using GWAS approach, followed by replication studies in Russian and Japanese elite athletes and functional validation using metabolomics analysis. The association of 476,728 SNPs of Illumina DrugCore Gene chip and endurance athlete status was investigated in 796 European international-level athletes (645 males, 151 females) by comparing allelic frequencies between athletes specialized in sports with high ( = 662) and low/moderate ( = 134) aerobic component. Replication of results was performed by comparing the frequencies of the most significant SNPs between 242 and 168 elite Russian high and low/moderate aerobic athletes, respectively, and between 60 elite Japanese endurance athletes and 406 controls. A meta-analysis has identified rs1052373 (GG homozygotes) in Myosin Binding Protein (; implicated in cardiac hypertrophic myopathy) gene to be associated with endurance athlete status ( = 1.43 × 10, odd ratio 2.2). Homozygotes carriers of rs1052373 G allele in Russian athletes had significantly greater VO than carriers of the AA + AG ( = 0.005). Subsequent metabolomics analysis revealed several amino acids and lipids associated with rs1052373 G allele (1.82 × 10) including the testosterone precursor androstenediol (3beta,17beta) disulfate. This is the first report of genome-wide significant SNP and related metabolites associated with elite athlete status. Further investigations of the functional relevance of the identified SNPs and metabolites in relation to enhanced athletic performance are warranted

The <i>ADORA2A</i> TT Genotype Is Associated with Anti-Inflammatory Effects of Caffeine in Response to Resistance Exercise and Habitual Coffee Intake

Caffeine is an adenosine A2A receptor (ADORA2A) antagonist with ergogenic and anti-inflammatory effects. Previous studies have reported that the ADORA2A gene regulates glutamate metabolism and immune responses, with the ADORA2A rs5751876 TT genotype (with high sensitivity to caffeine) showing larger ergogenic effect following caffeine ingestion. We therefore hypothesized that the TT genotype would be associated with greater anti-inflammatory effects of caffeine in response to exercise, and with higher coffee intake in physically active individuals. The aim of the present study was twofold: (1) to investigate the association of the ADORA2A variant with the anti-inflammatory effects of caffeine in response to intense resistance exercise (RE), and (2) to analyze the association of the rs5751876 with coffee intake in physically active individuals (n = 134). Fifteen resistance-trained athletes participated in a randomized, double-blind, placebo-controlled cross-over study, where they consumed 6 mg/kg of caffeine or placebo one hour prior to performing an RE protocol. Blood samples were taken immediately from the arterial vein before, immediately after, and 15 min after RE for the analysis of inflammatory markers myeloperoxidase (MPO) and acetylcholinesterase (AChE). We found that the ADORA2A TT genotype carriers experienced lower exercise-induced inflammatory responses (p ADORA2A TT genotype was positively associated with coffee intake (p = 0.0143; irrespective of CYP1A2 rs762551 polymorphism). In conclusion, we found that the ADORA2A gene polymorphism is associated with anti-inflammatory effects of caffeine in response to resistance exercise, as well as with habitual coffee intake in physically active individuals

The GALNTL6 Gene rs558129 Polymorphism Is Associated With Power Performance

The GALNTL6 gene rs558129 polymorphism is associated with power performance. J Strength Cond Res XX(X): 000-000, 2020-The largest genome-wide association study to date in sports genomics showed that endurance athletes were 1.23 times more likely to possess the C allele of the single nucleotide polymorphism rs558129 of N-acetylgalactosaminyltransferase-like 6 gene (GALNTL6), compared with controls. Nevertheless, no further study has investigated GALNTL6 gene in relation to physical performance. Considering that previous research has shown that the same polymorphism can be associated with both endurance and power phenotypes (ACTN3, ACE, and PPARA), we investigated the association between GALNTL6 rs558129 polymorphism and power performance. According to this objective we conducted 2 global studies regarding 2 different communities of athletes in Spain and Russia. The first study involved 85 Caucasian physically active men from the north of Spain to perform a Wingate anaerobic test (WAnT). In the second study we compared allelic frequencies between 173 Russian power athletes (49 strength and 124 speed-strength athletes), 169 endurance athletes, and 201 controls. We found that physically active men with the T allele of GALNTL6 rs558129 had 5.03-6.97% higher power values compared with those with the CC genotype (p < 0.05). Consistent with these findings, we have shown that the T allele was over-represented in power athletes (37.0%) compared with endurance athletes (29.3%; OR = 1.4, p = 0.032) and controls (28.6%; OR = 1.5, p = 0.015). Furthermore, the highest frequency of the T allele was observed in strength athletes (43.9%; odds ratio [OR] = 1.9, p = 0.0067 compared with endurance athletes; OR = 2.0, p = 0.0036 compared with controls). In conclusion, our data suggest that the GALNTL6 rs558129 T allele can be favorable for anaerobic performance and strength athletes. In addition, we propose a new possible functional role of GALNTL6 rs558129, gut microbiome regarding short-chain fatty acid regulation and their anti-inflammatory and resynthesis functions. Nevertheless, further studies are required to understand the mechanisms involved.Sin financiación3.775 JCR (2020) Q2, 25/88 Sport Sciences1.569 SJR (2020) Q1, 236/2448 Medicine (miscellaneous)No data IDR 2019UE

Exome-Wide Association Study of Competitive Performance in Elite Athletes

The aim of the study was to identify genetic variants associated with personal best scores in Turkish track and field athletes and to compare allelic frequencies between sprint/power and endurance athletes and controls using a whole-exome sequencing (WES) approach, followed by replication studies in independent cohorts. The discovery phase involved 60 elite Turkish athletes (31 sprint/power and 29 endurance) and 20 ethnically matched controls. The replication phase involved 1132 individuals (115 elite Russian sprinters, 373 elite Russian endurance athletes (of which 75 athletes were with VO2max measurements), 209 controls, 148 Russian and 287 Finnish individuals with muscle fiber composition and cross-sectional area (CSA) data). None of the single nucleotide polymorphisms (SNPs) reached an exome-wide significance level (p 2.3 x 10(-7)) in genotype-phenotype and case-control studies of Turkish athletes. However, of the 53 nominally (p 0.05) associated SNPs, four functional variants were replicated. The SIRT1 rs41299232 G allele was significantly over-represented in Turkish (p = 0.047) and Russian (p = 0.018) endurance athletes compared to sprint/power athletes and was associated with increased VO2max (p = 0.037) and a greater proportion of slow-twitch muscle fibers (p = 0.035). The NUP210 rs2280084 A allele was significantly over-represented in Turkish (p = 0.044) and Russian (p = 0.012) endurance athletes compared to sprint/power athletes. The TRPM2 rs1785440 G allele was significantly over-represented in Turkish endurance athletes compared to sprint/power athletes (p = 0.034) and was associated with increased VO2max (p = 0.008). The AGRN rs4074992 C allele was significantly over-represented in Turkish sprint/power athletes compared to endurance athletes (p = 0.037) and was associated with a greater CSA of fast-twitch muscle fibers (p = 0.024). In conclusion, we present the first WES study of athletes showing that this approach can be used to identify novel genetic markers associated with exercise- and sport-related phenotypes.Gazi University Rectorate (Scientific Research Projects Coordination's Unit) [TCD-2021-7116]This research received no external funding

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 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