Heritability estimates of endurance-related phenotypes: A systematic review and meta-analysis.

The aim of this study was to clarify heritability estimates for endurance-related phenotypes and the underlying factors affecting these estimates. A systematic literature search was conducted for studies reporting heritability estimates of endurance-related phenotypes using the PubMed database (up to 30 September 2016). Studies that estimated the heritability of maximal oxygen uptake (V˙O2max), submaximal endurance phenotypes, and endurance performance were selected. The weighted mean heritability for endurance-related phenotypes was calculated using a random-effects model. A total of 15 studies were selected via a systematic review. Meta-analysis revealed that the weighted means of the heritability of V˙O2max absolute values and those adjusted for body weight and for fat-free mass were 0.68 (95% CI: 0.59-0.77), 0.56 (95% CI: 0.47-0.65), and 0.44 (95% CI: 0.13-0.75), respectively. There was a significant difference in the weighted means of the heritability of V˙O2max across these different adjustment methods (P < .05). Moreover, there was evidence of statistical heterogeneity in the heritability estimates among studies. Meta-regression analysis revealed that sex could partially explain the heterogeneity in the V˙O2max heritability estimates adjusted by body weight. For submaximal endurance phenotypes and endurance performance, the weighted mean heritabilities were 0.49 (95% CI: 0.33-0.65) and 0.53 (95% CI: 0.27-0.78), respectively. There was statistically significant heterogeneity in the heritability estimates reported among the studies, and we could not identify the specific factors explaining the heterogeneity. Although existing studies indicate that genetic factors account for 44%-68% of the variability in endurance-related phenotypes, further studies are necessary to clarify these values.

Association analysis of the ACTN3 R577X polymorphism with passive muscle stiffness and muscle strain injury.

Passive muscle stiffness is considered to be a major factor affecting joint flexibility and is thought to relate to the occurrence of muscle strain injury. In skinned muscle fiber experiments, the R577X polymorphism of the α-actinin-3 gene (ACTN3) has been associated with passive muscle stiffness. Our primary purpose was to clarify whether the ACTN3 R577X polymorphism influences passive stiffness of human muscle in vivo. We also examined whether the ACTN3 R577X polymorphism is associated with the occurrence of hamstring strain injury. Seventy-six healthy young male subjects were genotyped for the ACTN3 R577X (rs1815739) polymorphism. Shear modulus (an index of stiffness) of each hamstring muscle (biceps femoris, semitendinosus, and semimembranosus) was assessed using ultrasound shear wave elastography, and history of hamstring strain injury was collected via a questionnaire. The muscle shear moduli of the semitendinosus and semimembranosus were significantly higher in R-allele (RR + RX genotype) carriers than in XX genotype carriers, whereas the shear modulus of the biceps femoris did not differ among the ACTN3 R577X genotypes. Frequency of past hamstring strain injury also did not differ between the 3 genotypes nor between the R-allele and XX genotype carriers. This study indicates that RR and RX genotypes of the ACTN3 R577X polymorphism (corresponding to the presence of α-actinin-3 in type II muscle fibers) are associated with increased passive muscle stiffness of the human hamstring in vivo. However, this altered mechanical property might not affect the risk of hamstring muscle strain injury.

Heritability estimates of muscle strength-related phenotypes: A systematic review and meta-analysis.

The purpose of this study was to clarify the heritability estimates of human muscle strength-related phenotypes (H2 -msp). A systematic literature search was conducted using PubMed (through August 22, 2016). Studies reporting the H2 -msp for healthy subjects in a sedentary state were included. Random-effects models were used to calculate the weighted mean heritability estimates. Moreover, subgroup analyses were performed based on phenotypic categories (eg, grip strength, isotonic strength, jumping ability). Sensitivity analyses were also conducted to investigate potential sources of heterogeneity of H2 -msp, which included age and sex. Twenty-four articles including 58 measurements were included in the meta-analysis. The weighted mean H2 -msp for all 58 measurements was 0.52 (95% confidence intervals [CI]: 0.48-0.56), with high heterogeneity (I2 =91.0%, P<.001). Subgroup analysis showed that the heritability of isometric grip strength, other isometric strength, isotonic strength, isokinetic strength, jumping ability, and other power measurements was 0.56 (95% CI: 0.46-0.67), 0.49 (0.47-0.52), 0.49 (0.32-0.67), 0.49 (0.37-0.61), 0.55 (0.45-0.65), and 0.51 (0.31-0.70), respectively. The H2 -msp decreased with age (P<.05). In conclusion, our results indicate that the influence of genetic and environmental factors on muscle strength-related phenotypes is comparable. Moreover, the role of environmental factors increased with age. These findings may contribute toward an understanding of muscle strength-related phenotypes.

CNTFR Genotype and Sprint/power Performance: Case-control Association and Functional Studies.

The aim of this study was to investigate whether rs41274853 in the 3'-untranslated region of the ciliary neurotrophic factor receptor gene (CNTFR) is associated with elite sprint/power athletic status and assess its functional significance. A total of 211 Japanese sprint/power track and field athletes (62 international, 72 national, and 77 regional athletes) and 814 Japanese controls were genotyped at rs41274853. Luciferase reporter assay was conducted to investigate whether this C-to-T polymorphism affects binding of microRNA miR-675-5p to this region. The TT genotype was significantly more frequent among international sprint/power athletes (19.4%) than in the controls after Bonferroni correction (7.9%, P=0.036, OR=2.81 [95% CI: 1.43-5.55]). Furthermore, in non-athletic young/middle-aged men (n=132), TT genotype carriers exhibited significantly greater leg extension power (26.6±5.4 vs. 24.0±5.4 W/kg BW, P=0.019) and vertical jump performance (50.1±6.9 vs. 47.9±7.5 cm, P=0.047) than the CC+CT genotype carriers. Reporter assays revealed that the miR-675-5p binds to this polymorphic region within the CNTFR mRNA, irrespective of the rs41274853 allele present. Although the functional significance of the rs41274853 polymorphism remains unclear, the CNTFR is one of the candidate genes contributing to sprint/power performance.