Advances in exercise, fitness, and performance genomics in 2010

Abstract

This review of the exercise genomics literature emphasizes the strongest articles published in 2010 as defined by sample size, quality of phenotype measurements, quality of the exercise program or physical activity exposure, study design, adjustment for multiple testing, quality of genotyping, and other related study characteristics. One study on voluntary running wheel behavior was performed in 448 mice from 41 inbred strains. Several quantitative trait loci for running distance, speed, and duration were identified. Several studies on the alpha-3 actinin (ACTN3) R577X nonsense polymorphism and the angiotensin-converting enzyme (ACE) I/D polymorphism were reported with no clear evidence for a joint effect, but the studies were generally underpowered. Skeletal muscle RNA abundance at baseline for 29 transcripts and 11 single nucleotide polymorphisms (SNPs) were both found to be predictive of the V˙O2max response to exercise training in one report from multiple laboratories. None of the 50 loci associated with adiposity traits are known to influence physical activity behavior. However, physical activity seems to reduce the obesity-promoting effects of at least 12 of these loci. Evidence continues to be strong for a role of gene-exercise interaction effects on the improvement in insulin sensitivity after exposure to regular exercise. SNPs in the cAMP-responsive element binding position 1 (CREB1) gene were associated with training-induced HR response, in the C-reactive protein (CRP) gene with training-induced changes in left ventricular mass, and in the methylenetetrahydrofolate reductase (MTHFR) gene with carotid stiffness in low-fit individuals. We conclude that progress is being made but that high-quality research designs and replication studies with large sample sizes are urgently needed.

Figure 1

Association between the genetic predisposition score (sum of BMI-increasing alleles from 12 BMI loci) with BMI in all individuals (solid black line), in sedentary individuals (dashed grey line), and in physically active individuals (solid grey line). The bars represent the number of individuals at every unit of the predisposition score. Effect sizes expressed in grams assume a height of 1.70 m. Adapted from Li S, Zhao JH, Luan Ja, et al. Physical activity attenuates the genetic predisposition to obesity in 20,000 men and women from EPIC-Norfolk prospective population study. PLoS Med. 2010;7:e1000332.

Figure 2

Carotid β-stiffness (β-stiffness) of each fitness group and genotype of MTHFR gene polymorphism (C677T; CC, CT, TT genotypes) of 763 subjects in a cross-sectional study. Subjects were divided into low cardiorespiratory fitness (Low-Fit) and high cardiorespiratory fitness (High-Fit) groups, with the dividing line set at the median value of peak oxygen uptake in each sex and decade of age as a cutoff. Differences in β-stiffness between each fitness group and genotype were assessed by an analysis of covariance (ANCOVA) model that included age as a covariate. Data are expressed as means ± SE for numbers of subjects indicated in the bar. AU, arbitrary units; NS, not significant. From Iemitsu M, Murakami H, Sanada K, et al. Lack of carotid stiffening associated with MTHFR 677TT genotype in cardiorespiratory fit adults. Physiol Genomics. 2010;42:259–65. Used with permission of the American Physiological Society.

Figure 3

Panel A. Number of subjects needed for a given effect size for a continuous trait assuming 80% statistical power, an additive model, and three alpha levels: 0.05 (1 SNP), 0.0001 (500 SNPs), and 5×10⁻⁸ (1 million SNP GWAS). Panel B. Number of subjects needed for a given effect size (measured as an odds ratio [OR]) for a case-control design assuming 80% statistical power, a minor allele frequency (MAF) of 20%, an additive model, and three alpha levels: 0.05 (1 SNP), 0.0001 (500 SNPs), and 5×10⁻⁸ (1 million SNP GWAS).

Figure 3

Panel A. Number of subjects needed for a given effect size for a continuous trait assuming 80% statistical power, an additive model, and three alpha levels: 0.05 (1 SNP), 0.0001 (500 SNPs), and 5×10⁻⁸ (1 million SNP GWAS). Panel B. Number of subjects needed for a given effect size (measured as an odds ratio [OR]) for a case-control design assuming 80% statistical power, a minor allele frequency (MAF) of 20%, an additive model, and three alpha levels: 0.05 (1 SNP), 0.0001 (500 SNPs), and 5×10⁻⁸ (1 million SNP GWAS).