No Evidence of a Common DNA Variant Profile Specific to World Class Endurance Athletes

There are strong genetic components to cardiorespiratory fitness and its response to exercise training. It would be useful to understand the differences in the genomic profile of highly trained endurance athletes of world class caliber and sedentary controls. An international consortium (GAMES) was established in order to compare elite endurance athletes and ethnicity-matched controls in a case-control study design. Genome-wide association studies were undertaken on two cohorts of elite endurance athletes and controls (GENATHLETE and Japanese endurance runners), from which a panel of 45 promising markers was identified. These markers were tested for replication in seven additional cohorts of endurance athletes and controls: from Australia, Ethiopia, Japan, Kenya, Poland, Russia and Spain. The study is based on a total of 1520 endurance athletes (835 who took part in endurance events in World Championships and/or Olympic Games) and 2760 controls. We hypothesized that world-class athletes are likely to be characterized by an even higher concentration of endurance performance alleles and we performed separate analyses on this subsample. The meta-analysis of all available studies revealed one statistically significant marker (rs558129 at GALNTL6 locus, p = 0.0002), even after correcting for multiple testing. As shown by the low heterogeneity index (I2 = 0), all eight cohorts showed the same direction of association with rs558129, even though p-values varied across the individual studies. In summary, this study did not identify a panel of genomic variants common to these elite endurance athlete groups. Since GAMES was underpowered to identify alleles with small effect sizes, some of the suggestive leads identified should be explored in expanded comparisons of world-class endurance athletes and sedentary controls and in tightly controlled exercise training studies. Such studies have the potential to illuminate the biology not only of world class endurance performance but also of compromised cardiac functions and cardiometabolic diseases

Molecular and seroepidemiological investigation of Сoxiella burnetii and spotted fever group rickettsiae in the southern region of Kazakhstan

Ticks are involved in the circulation of a number of human pathogens, including spotted fever group (SFG) Rickettsia spp. and Coxiella burnetii. Little is known about the occurrence of these microorganisms in the southern region of Kazakhstan. In 2018–2022, a total of 726 ticks were collected from bitten humans, livestock, and vegetation in four oblasts of the southern region of Kazakhstan and subjected to DNA extraction. The overall infection rate of Coxiella spp. and Rickettsia spp. in the ticks was 3.3% (24/726) and 69.9% (300/429), respectively. Phylogenetic analysis of ompA and gltA genes revealed the presence of three pathogenic SFG rickettsiae: Candidatus R. tarasevichiae, R. aeschlimannii and R. raoultii in ticks collected from bitten humans. In addition, Candidatus R. barbariae was detected in six Rhipicephalus turanicus ticks for the first time in Kazakhstan. To determine the seroprevalence of C. burnetii infection, we performed a serological analysis of samples collected from 656 domestic ruminants (cattle, sheep, and goats) in the region. Overall, 23.5% (154/656) of the animals tested were positive for IgG against C. burnetii. Seroprevalence at the herd level was 54% (28/52). Goats (43%; 12/28; odds ratio (OD) = 28.9, p < 0.05) and sheep (31.9%; 137/430; OD = 18.1, p < 0.05) had higher seroprevalence than cattle (2.5%; 5/198). Among the risk factors considered in this study, age (p = 0.003) and the oblast in which the animals were sampled (p = 0.049) were statistically associated with seropostivity for Q fever in sheep, according to the results of multivariate logistic regression analysis. Seroprevalence ranged from 0% to 55.5% in animals in different districts of the southern region of Kazakhstan. Active C. burnetii bacteremia was detected in four of 154 (2.6%) seropositive animals. The data obtained provide strong evidence of the presence of pathogenic rickettsiae and C. burnetii in the southern region of Kazakhstan and emphasize the need to improve epidemiological surveillance in the region

Discovery Phase: Most Significant Associations of CardioMetabochip SNPs and All Endurance Athletes as well as World-Class Athletes versus Controls in the GENATHLETE Cohort.

<p>Discovery Phase: Most Significant Associations of CardioMetabochip SNPs and All Endurance Athletes as well as World-Class Athletes versus Controls in the GENATHLETE Cohort.</p

Results for Replication Meta-Analysis and for Individual Cohorts for All Athletes and Controls of European Descent; Results in bold type are for p≤0.05.

<p>Results for Replication Meta-Analysis and for Individual Cohorts for All Athletes and Controls of European Descent; Results in bold type are for p≤0.05.</p

Manhattan Plot of the Association P Values for the CardioMetabochip SNP Differences in Allele Frequencies Between Endurance Athletes and Sedentary Controls in GENATHLETE.

<p>(A) Athletes with VO₂max ≥ 75 ml O₂/kg/min (N = 315) vs. Controls (N = 320). (B) Elite Athletes with VO₂max ≥ 78 ml O₂/kg/min (N = 168) vs. Controls (N = 320).</p

Results for the Replication in Athletes and Controls from Kenya and Ethiopia; Results in bold type are for p ≤0.05.

<p>Results for the Replication in Athletes and Controls from Kenya and Ethiopia; Results in bold type are for p ≤0.05.</p

Results for the Meta-analysis of All Studies of World-class Athletes and Controls (GENATHLETE, Japan, Australia, Poland, Russia, Spain); Results in bold type are for p ≤ 0.05.

<p>Results for the Meta-analysis of All Studies of World-class Athletes and Controls (GENATHLETE, Japan, Australia, Poland, Russia, Spain); Results in bold type are for p ≤ 0.05.</p

Number of Athletes and Controls of Each Study Participating in the GAMES Consortium.

<p>Number of Athletes and Controls of Each Study Participating in the GAMES Consortium.</p

Results for the Meta-analysis of All Studies of All Athletes and Controls (GENATHLETE, Japan, Australia, Poland, Russia, Spain, Kenya, and Ethiopia); Results in bold type are for p ≤ 0.05.

<p>Results for the Meta-analysis of All Studies of All Athletes and Controls (GENATHLETE, Japan, Australia, Poland, Russia, Spain, Kenya, and Ethiopia); Results in bold type are for p ≤ 0.05.</p

Manhattan plot of -log10(p) values against genomic position for association of elite endurance status with markers in 22 autosomes in Japanese.

<p>Red line refers to p = 5x10-6; blue line refers to p = 5x10-5.</p