title: Genomics of elite sporting performance: what little we know and necessary advances.
abstract: Numerous reports of genetic associations with performance- and injury-related phenotypes have been published over the past three decades; these studies have employed primarily the candidate gene approach to identify genes that associate with elite performance or with variation in performance-and/or injury-related traits. Although generally with small effect sizes and heavily prone to type I statistic error, the number of candidate genetic variants that can potentially explain elite athletic status, injury predisposition, or indeed response to training will be much higher than that examined by numerous biotechnology companies. Priority should therefore be given to applying whole genome technology to sufficiently large study cohorts of world-class athletes with adequately measured phenotypes where it is possible to increase statistical power. Some of the elite athlete cohorts described in the literature might suffice, and collectively, these cohorts could be used for replication purposes. Genome-wide association studies are ongoing in some of these cohorts (i.e., Genathlete, Russian, Spanish, Japanese, United States, and Jamaican cohorts), and preliminary findings include the identification of one single nucleotide polymorphism (SNP; among more than a million SNPs analyzed) that associates with sprint performance in Japanese, American (i.e., African American), and Jamaican cohorts with a combined effect size of ~2.6 (P-value <5×10(-7)) and good concordance with endurance performance between select cohorts. Further replications of these signals in independent cohorts will be required, and any replicated SNPs will be taken forward for fine-mapping/targeted resequencing and functional studies to uncover the underlying biological mechanisms. Only after this lengthy and costly process will the true potential of genetic testing in sport be determined.
authors.affiliation: Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Guan
authors.initials: G
authors.lastname: Wang
authors.forename: Sandosh
authors.initials: S
authors.lastname: Padmanabhan
authors.forename: Bernd
authors.initials: B
authors.lastname: Wolfarth
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Fuku
authors.forename: Alejandro
authors.initials: A
authors.lastname: Lucia
authors.forename: Ildus I
authors.initials: II
authors.lastname: Ahmetov
authors.forename: Pawel
authors.initials: P
authors.lastname: Cieszczyk
authors.forename: Malcolm
authors.initials: M
authors.lastname: Collins
authors.forename: Nir
authors.initials: N
authors.lastname: Eynon
authors.forename: Vassilis
authors.initials: V
authors.lastname: Klissouras
authors.forename: Alun
authors.initials: A
authors.lastname: Williams
authors.forename: Yannis
authors.initials: Y
authors.lastname: Pitsiladis
mesh_terms: D000185:Actinin / Q000235:genetics; D056352:Athletes; D054874:Athletic Performance; D005820:Genetic Testing; D055106:Genome-Wide Association Study; D006801:Humans; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012420:Running
chemical_list: C118456:ACTN3 protein, human; D000185:Actinin; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A
keywords: ACE/ACTN3 polymorphisms; candidate gene association study; complex trait; elite performance; genome-wide association study; single nucleotide polymorphism