Sports genetics moving forward: lessons learned from medical research

Abstract

Sports genetics can take advantage of lessons learned from human disease genetics. By righting past mistakes and increasing scientific rigor, we can magnify the breadth and depth of knowledge in the field. We present an outline of challenges facing sports genetics in the light of experiences from medical research. Sports performance is complex, resulting from a combination of a wide variety of different traits and attributes. Improving sports genetics will foremost require analyses based on detailed phenotyping. To find widely valid, reproducible common variants associated with athletic phenotypes, study sample sizes must be dramatically increased. One paradox is that in order to confirm relevance, replications in specific populations must be undertaken. Family studies of athletes may facilitate the discovery of rare variants with large effects on athletic phenotypes. The complexity of the human genome, combined with the complexity of athletic phenotypes, will require additional metadata and biological validation to identify a comprehensive set of genes involved. Analysis of personal genetic and multiomic profiles contribute to our conceptualization of precision medicine; the same will be the case in precision sports science. In the refinement of sports genetics it is essential to evaluate similarities and differences between sexes and among ethnicities. Sports genetics to date have been hampered by small sample sizes and biased methodology, which can lead to erroneous associations and overestimation of effect sizes. Consequently, currently available genetic tests based on these inherently limited data cannot predict athletic performance with any accuracy.

Deep-targeted exon sequencing reveals renal polymorphisms associate with postexercise hypotension among African Americans

“…We recently conducted a meta-analysis of candidate gene association studies examining the BP response to acute (i.e., PEH) and chronic (i.e., training) aerobic exercise and found that Angiotensiogen (AGT) rs699 emerged as the only promising variant to explore further (Bruneau et al 2015). This finding substantiates a major concern of candidate gene association studies that examine the response of health-related phenotypes to exercise; that is, most statistically significant findings fail to replicate due to a variety of factors that include the lack of standardized protocols, statistical adjustments for multiple comparisons, and adequately powered samples (Bouchard 2011;Bouchard et al 2012;Ash et al 2013a;Bruneau et al 2015;Mattsson et al 2016).…”

“…In addition, we instituted methodological strategies to increase the statistical power to detect renal genotype-BP associations should they exist (Bouchard 2011;Ash et al 2013a;Bruneau et al 2015;Mattsson et al 2016). These strategies included a repeated measure design among the same individuals that increased the number of observations per subject by 19 hourly time points, a focused inquiry of polymorphisms with a prioritized panel of genes that reduced the search space within the genome, performing high throughput exon sequencing to focus on functional regions of the gene, and inclusion of the same standardized protocols and methods in our discovery phase and replication studies.…”

Letter to the editor: A genetic-based algorithm for personalized resistance training

“…ACTN3 and ACE ) polymorphisms have been associated with an acceptable level of replication with endurance or power athletic performance, and none of these associations are strong enough to predict elite sports performance or trainability [14, 23, 24]. Currently, there is lack of scientific evidence supporting the predictive values of genetic tests (direct-to-consumer) for prescription of exercise training programmes, or for that matter, talent identification.…”

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“…To improve the effectiveness of sports genetics primarily will require analysis based on a detailed full [17,18].…”

“…Angiotensin-converting enzyme gene (ACE) which had concluded that one of the polymorphic alleles of ACE gene is allele-I provides tolerance, and allele-D -speed-power qualities of athlete, on the basis of higher frequency of alleles in athletes, successful in their respective sports in relation to the control group [17]. However, in the future, a number of authors will find no differences in the frequency of occurrence of genotypes in athletes and people who are not involved in sports [18,19]. Nevertheless, differences will be appeared in the analysis of the study in athletes' genotypes, specializing in several sport fields [20].…”