Using the model originally developed by Williams and Folland (J Physiol 586: 113-121, 2008), we determined 1) a "total genotype score" (TGS, from the accumulated combination of the 6 polymorphisms, with a maximum value of "100" for the theoretically optimal polygenic score) in a group of elite power athletes, endurance athletes, and nonathletic controls, and 2) the probability for the occurrence of Spanish individuals with the "perfect" power-oriented profile (i.e., TGS = 100). We analyzed six polymorphism that are candidates to explain individual variations in elite power athletic status or power phenotypes (ACE I/D, ACTN3 R577X, AGT Met235Thr, GDF-8 K153R, IL6 -174 G/C, and NOS3 -786T>C) in 53 elite track and field power athletes (jumpers, sprinters), 100 nonathletic controls, and 100 elite endurance athletes (distance runners and road cyclists) (all Spanish Caucasian males). The mean TGS was significantly higher in power athletes (70.8 +/- 17.3) compared with endurance athletes (60.4 +/- 15.9; P < 0.001) and controls (63.3 +/- 13.2; P = 0.012), whereas it did not differ between the latter two groups (P = 0.366). A total of five power athletes (9.4%, all sprinters) had a theoretically "optimal" TGS of 100 vs. 0 subjects in the other two groups. The probability of a Spanish individual possessing a theoretically optimal polygenic profile for up to the six candidate polymorphisms we studied was very small, i.e., approximately 0.2% (or 1 in 500 Spanish individuals). We have identified a polygenic profile that allows us, at least partly, to distinguish elite power athletes from both endurance athletes and nonathletic population.

The NOS3 gene is a candidate to explain individual variations in health and exercise related phenotypes. We compared genotypic and allelic frequencies of the NOS3 -786 T/C polymorphism (rs2070744) in three groups of men of the same Caucasian (Spanish) descent: (i) elite endurance athletes (cyclists, runners; N = 100); (ii) elite power athletes (jumpers, throwers, sprinters; N = 53) and (iii) non-athletic controls (N = 100). The frequency of the TT genotype was significantly higher in power athletes (57%) than in the endurance (33%, P = 0.017) or control group (34%, P = 0.026). The frequency of the T allele was also higher in power sportsmen (71%) than in their endurance (55%, P = 0.003) and control referents (56%, P = 0.015). No differences were observed between control and endurance groups. In summary, the -786 T/C polymorphism of the NOS3 gene seems to be associated with elite performance in power-oriented athletic events (throwing, jumping, sprinting), with the T allele exerting a beneficial effect. The mechanism by which this allele variant might benefit power performance remains to be elucidated.

In this study, genotype frequencies of several polymorphisms that are candidates to influence sports performance (ie, ACTN3 R577X, ACE ID, PPARGC1A Gly482Ser, AMPD1 C34T, CKMM 985bp/1170bp and GDF8 (myostatin) K153R) were compared in 123 nonathletic controls, 50 professional cyclists, 52 Olympic-class runners and 39 world-class rowers (medallists in world championships, lightweight category). Significant differences in genotype distributions among the groups were not found except for the ACE gene, that is, lower (p<0.05) proportion of II in rowers (10.3%) than in the total subject population (22.3%). In summary, sports performance is likely polygenic with the combined effect of hundreds of genetic variants, one possibly being the ACE ID polymorphism (at least in the sports studied here), but many others remain to be identified.

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The goal of our study was to discriminate potential genetic differences between humans who are in both endpoints of the sports performance continuum (i.e. world-class endurance vs power athletes). We used DNA-microarray technology that included 36 genetic variants (within 20 different genes) to compare the genetic profile obtained in two cohorts of world-class endurance (N=100) and power male athletes (N=53) of the same ethnic origin. Stepwise multivariate logistic regression showed that the rs1800795 (IL6-174 G/C), rs1208 (NAT2 K268R) and rs2070744 (NOS3-786 T/C) polymorphisms significantly predicted sport performance (model χ(2) =25.3, df=3, P-value <0.001). Receiver-operating characteristic (ROC) curve analysis showed a significant discriminating accuracy of the model, with an area under the ROC curve of 0.72 (95% confidence interval: 0.66-0.81). The contribution of the studied genetic factors to sports performance was 21.4%. In summary, although an individual's potential for excelling in endurance or power sports can be partly predicted based on specific genetic variants (many of which remain to be identified), the contribution of complex gene-gene interactions, environmental factors and epigenetic mechanisms are also important contributors to the "complex trait" of being an athletic champion. Such trait is likely not reducible to defined genetic polymorphisms.

In this study, allele and genotype frequencies of the ADRB1 Arg389Gly (rs1801253), ADRB2 Gly16Arg (rs1042713) and Gln27Glu (rs1042714), and ADRB3 Trp64Arg (rs4994) variations were compared in the following three groups of Spanish (Caucasian) men: (1) world-class endurance athletes (E; runners and cyclists, n=100), (2) elite power athletes (P; sprinters, jumpers and throwers, n=53) and (3) non-athletic controls (C; n=100). No significant differences were observed in genotype and allele distributions among the study groups except for the ADRB3 Trp64Arg polymorphism in E versus C (27% vs 8% of carriers of the Arg allele in E and C, p<0.001; frequency of the minor Arg (C) allele of 14% vs 4% in E and C, p=0.001). Heterozygosity for the ADRB3 Trp64Arg polymorphism seems to be associated with elite endurance performance, while other variants of the β-adrenergic receptors' genes do not seem to significantly influence top-level sports performance, at least in athletes of Spanish origin.

We compared a polygenic profile that combined 33 disease risk-related mutations and polymorphisms among nonathletic healthy control subjects and elite endurance athletes. The study sample comprised 100 healthy Spanish male nonathletic (sedentary) control subjects and 100 male elite endurance athletes. We analyzed 33 disease risk-related mutations and polymorphisms. We computed a health-related total genotype score (TGS, 0-100) from the accumulated combination of the 33 variants. We did not observe significant differences in genotype or allele distributions among groups, except for the rs4994 polymorphism (P < 0.001). The computed health-related TGS was similar among groups (23.8 +/- 1.0 vs. 24.2 +/- 0.8 in control subjects and athletes, respectively; P = 0.553). Similar results were obtained when computing specific TGSs for each main disease category (cardiovascular disease and cancer). We observed no evidence that male elite endurance athletes are genetically predisposed to have lower disease risk than matched nonathletic control subjects.

Our study purpose was to compare a disease-related polygenic profile that combined a total of 62 genetic variants among (i) people reaching exceptional longevity, i.e., centenarians (n=54, 100-108 years, 48 women) and (ii) ethnically matched healthy controls (n=87, 19-43 years, 47 women). We computed a 'global' genotype score (GS) for 62 genetic variants (mutations/polymorphisms) related to cardiometabolic diseases, cancer or exceptional longevity, and also specific GS for main disease categories (cardiometabolic risk and cancer risk, including 36 and 24 genetic variations, respectively) and for exceptional longevity (7 genetic variants). The 'global' GS was similar among groups (centenarians: 31.0±0.6; controls 32.0±0.5, P=0.263). We observed that the GS for hypertension, cancer (global risk), and other types of cancer was lower in the centenarians group compared with the control group (all P<0.05), yet the difference became non significant after adjusting for sex. We observed significant between-group AGE (2012) 810-13.839), whereas the likelihood of having the GSTMI low-risk (functional) allele was similar in both groups (OR 1.295; 95% CI, 0.868 -1.931). In conclusion, we found preliminary evidence that Spanish centenarians have a lower genetic predisposition for cancer risk. The wild-type (i.e., functional) genotype of GSTT1, which is associated with lower cancer risk, might be associated with exceptional longevity, yet further studies with larger sample sizes must confirm these findings.