<strong>GENOME-WIDE ASSOCIATION STUDY IDENTIFIES THREE NOVEL GENETIC MARKERS ASSOCIATED WITH ELITE ENDURANCE PERFORMANCE </strong>

Abstract

To investigate the association between multiple single-nucleotide polymorphisms (SNPs), aerobic performance and elite endurance athlete status in Russians. By using GWAS approach, we examined the association between 1,140,419 SNPs and relative maximal oxygen consumption rate (V.O2max) in 80 international-level Russian endurance athletes (46 males and 34 females). To validate obtained results, we further performed case-control studies by comparing the frequencies of the most significant SNPs (with P < 10−5-10−8) between 218 endurance athletes and opposite cohorts (192 Russian controls, 1367 European controls, and 230 Russian power athletes). Initially, six ‘endurance alleles’ were identified showing discrete associations with V.O2max both in males and females. Next, case-control studies resulted in remaining three SNPs (NFIA-AS2 rs1572312, TSHR rs7144481, RBFOX1 rs7191721) associated with endurance athlete status. The C allele of the most significant SNP, rs1572312, was associated with high values of V.O2max (males: P = 0.0051; females: P = 0.0005). Furthermore, the frequency of the rs1572312 C allele was significantly higher in elite endurance athletes (95.5%) in comparison with non-elite endurance athletes (89.8%, P = 0.0257), Russian (88.8%, P = 0.007) and European (90.6%, P = 0.0197) controls and power athletes (86.2%, P = 0.0005). The rs1572312 SNP is located on the nuclear factor I A antisense RNA 2 (NFIA-AS2) gene which is supposed to regulate the expression of the NFIA gene (encodes transcription factor involved in activation of erythropoiesis and repression of the granulopoiesis). Our data show that the NFIA-AS2 rs1572312, TSHR rs7144481 and RBFOX1 rs7191721 polymorphisms are associated with aerobic performance and elite endurance athlete status.

Current Progress in Sports Genomics

“…Additionally, the frequency of the C allele was significantly higher in elite endurance athletes in comparison with nonelite endurance athletes, Russian and European controls, and power athletes [5]. Consistent with the hypothesis, the authors also reported that the C allele was associated with activation of erythropoiesis (high level of hemoglobin, high number of reticulocytes and erythrocytes), while the A allele with activated granulopoiesis (high number of neutrophils and greater leukocyte/erythrocyte ratio).…”

“…By performing GWAS of 80 Russian endurance athletes, Ahmetov et al [5] have shown that the rs157231 CC genotype of the NFIA-AS2 gene was associated with high VO 2max in three subgroups of athletes (male and female middle and short endurance athletes; female long endurance athletes). Additionally, the frequency of the C allele was significantly higher in elite endurance athletes in comparison with nonelite endurance athletes, Russian and European controls, and power athletes [5].…”

“…By performing GWAS of 80 Russian endurance athletes, Ahmetov et al [5] have shown that the middle and short endurance athletes of both genders, as well as all female endurance athletes with the G allele of the rs7191721 G/A polymorphism had greater aerobic capacity. Additionally, the G allele was overrepresented in endurance athletes when compared to power athletes.…”

“…By performing GWAS of 80 Russian endurance athletes, Ahmetov et al [5] have shown that the C allele of the TSHR gene rs7144481 T/C polymorphism was associated with greater aerobic capacity (discovery P value-8.92 Â 10 À8 ) in three subgroups of athletes (male long endurance athletes; all male and all female athletes). The significance of this SNP was confirmed in case-control studies (higher frequency of the C allele in elite endurance athletes in comparison with Russian and European controls).…”

“…One of the advantages of the GWAS approach is that it is unbiased with respect to genomic structure and previous knowledge of the trait (hypothesis free), in contrast to candidate gene studies, where knowledge of the trait is used to identify candidate loci contributing to the trait of interest [5].…”