No Evidence of a Common DNA Variant Profile Specific to World Class Endurance Athletes

PLoS One. 2016 Jan 29;11(1):e0147330. doi: 10.1371/journal.pone.0147330. eCollection 2016.


There are strong genetic components to cardiorespiratory fitness and its response to exercise training. It would be useful to understand the differences in the genomic profile of highly trained endurance athletes of world class caliber and sedentary controls. An international consortium (GAMES) was established in order to compare elite endurance athletes and ethnicity-matched controls in a case-control study design. Genome-wide association studies were undertaken on two cohorts of elite endurance athletes and controls (GENATHLETE and Japanese endurance runners), from which a panel of 45 promising markers was identified. These markers were tested for replication in seven additional cohorts of endurance athletes and controls: from Australia, Ethiopia, Japan, Kenya, Poland, Russia and Spain. The study is based on a total of 1520 endurance athletes (835 who took part in endurance events in World Championships and/or Olympic Games) and 2760 controls. We hypothesized that world-class athletes are likely to be characterized by an even higher concentration of endurance performance alleles and we performed separate analyses on this subsample. The meta-analysis of all available studies revealed one statistically significant marker (rs558129 at GALNTL6 locus, p = 0.0002), even after correcting for multiple testing. As shown by the low heterogeneity index (I2 = 0), all eight cohorts showed the same direction of association with rs558129, even though p-values varied across the individual studies. In summary, this study did not identify a panel of genomic variants common to these elite endurance athlete groups. Since GAMES was underpowered to identify alleles with small effect sizes, some of the suggestive leads identified should be explored in expanded comparisons of world-class endurance athletes and sedentary controls and in tightly controlled exercise training studies. Such studies have the potential to illuminate the biology not only of world class endurance performance but also of compromised cardiac functions and cardiometabolic diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Athletes*
  • DNA Copy Number Variations
  • Gene Expression
  • Gene Frequency
  • Genetic Heterogeneity*
  • Genetic Loci
  • Genetic Markers
  • Genome, Human*
  • Genome-Wide Association Study
  • Humans
  • Male
  • Maximal Expiratory Flow Rate / genetics
  • N-Acetylgalactosaminyltransferases / genetics
  • Oxygen Consumption / genetics
  • Physical Endurance / genetics*
  • Physical Fitness
  • Polymorphism, Single Nucleotide
  • Polypeptide N-acetylgalactosaminyltransferase
  • Sedentary Behavior


  • Genetic Markers
  • N-Acetylgalactosaminyltransferases

Associated data

  • figshare/10.6084/M9.FIGSHARE.1619893

Grants and funding

Partial funding for the study has been received from the Prince Faisal Prize awarded to Drs. C. Bouchard, T. Rankinen, M. Sarzynski and B. Wolfahrt. CB is partially funded by the John W. Barton Jr Chair in Genetics and Nutrition. The study in Russia was supported by a grant from the Federal Medical-Biological Agency (“Sportgen project”), The Spanish group (AL, CAM, CS, TY) was funded by Fondo de Investigaciones Sanitarias (grant # PI12/00914). Research in sports genetics to A. Lucia in Spain was funded by grants from the Consejo Superior de Deportes (CSD). This work in Japan was supported in part by grants from the programs Grants-in-Aid for Challenging Exploratory Research (24650414 to NF) from the Ministry of Education, Culture, Sports, Science and Technology; and by a grant-in-aid for scientific research from the Ministry of Health, Labor, and Welfare of Japan (to MM). No specific funding for this work was received for the studies performed in Australia, Poland, Kenya and Ethiopia. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.