Analysis Of Multiple Performance-associated Genetic Polymorphisms In Sprint And Endurance Running World Record Holders

Abstract

The probability for the occurrence of humans with the "perfect" polygenic profile for elite physical performance was calculated from the theoretically best accumulated combination of 23 genetic polymorphisms (Williams and Folland, J Physiol 586:113-121, 2008). PURPOSE: To compare the "observed" profiles of sprint and endurance running world record holders based on 24 previously published performance-associated genetic polymorphisms (PAPs). METHODS: Genotype scores (maximum value of 100 for the theoretically optimal polygenic score) for 12 sprint PAPs (IL15, CNTF, FST, IGF2, IL15RA-1, IL15RA-2, TNF, NR3C1, CNTFR, PPARA, ACTN3, ACE) and 14 endurance PAPs (PPARA, HIF1A, UCP3, ADRB2, ADRA2A, AMPD1, BDKRB2, CKM, HFE, PPARD-1, PPARD-2, PPARGC1A, UCP2, ACE) were determined in 4 sprint world record holders and 6 ethnically-matched controls and in 5 endurance running world record holders and 7 matched controls. RESULTS: The total genotype score in sprinters for the sprint PAPs tended to be higher than in endurance runners (54 [46-63]% (mean [range]) vs. 43 [33-50]%, P=0.09 assessed by Chi-square test), while there was no difference between sprinters and their controls. The total genotype score in endurance runners for the endurance PAPs was significantly higher than in sprinters (49 [43-57]% vs. 39 [32-46]%, P<0.05), while there was no difference between endurance runners and their controls. The total genotype score in sprinters for the endurance PAPs tended to be lower than their controls (39 [32-46]% vs. 47 [32-64]%, P=0.24). We also performed GWAS in 47 elite Jamaican sprinters and 47 ethnically-matched controls. From ∼1 million SNPs determined, 6058 differed significantly (P<0.001) between sprinters and controls. Two SNPs remained significantly associated with sprint performance after correcting for false discovery rate, while 1 SNP showed a similar trend. CONCLUSIONS: These trends are encouraging given the perceived lack of power of conventional gene-based association studies to detect multiple small but cumulative gene effects. However, an effect of ethnicity cannot be ruled out. The genotyping of athletes of the highest performance calibre such as world record holders, world champions and Olympians may circumvent the need for large cohorts (i.e. 20,000-100,000) in order to discover PAPs.