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Sports genomics is the scientific discipline that focuses on the organization and function of the genome in elite athletes, and aims to develop molecular methods for talent identification, personalized exercise training, nutritional need and prevention of exercise-related diseases. It postulates that both genetic and environmental factors play a key role in athletic performance and related phenotypes. This update on the panel of genetic markers (DNA polymorphisms) associated with athlete status and soft-tissue injuries covers advances in research reported in recent years, including one whole genome sequencing (WGS) and four genome-wide association (GWAS) studies, as well as findings from collaborative projects and meta-analyses. At end of 2020, the total number of DNA polymorphisms associated with athlete status was 220, of which 97 markers have been found significant in at least two studies (35 endurance-related, 24 power-related, and 38 strength-related). Furthermore, 29 genetic markers have been linked to soft-tissue injuries in at least two studies. The most promising genetic markers include HFE rs1799945, MYBPC3 rs1052373, NFIA-AS2 rs1572312, PPARA rs4253778, and PPARGC1A rs8192678 for endurance; ACTN3 rs1815739, AMPD1 rs17602729, CPNE5 rs3213537, CKM rs8111989, and NOS3 rs2070744 for power; LRPPRC rs10186876, MMS22L rs9320823, PHACTR1 rs6905419, and PPARG rs1801282 for strength; and COL1A1 rs1800012, COL5A1 rs12722, COL12A1 rs970547, MMP1 rs1799750, MMP3 rs679620, and TIMP2 rs4789932 for soft-tissue injuries. It should be appreciated, however, that hundreds and even thousands of DNA polymorphisms are needed for the prediction of athletic performance and injury risk.

The substantial decline in skeletal muscle mass, strength, and gait speed is a sign of severe sarcopenia, which may partly depend on genetic risk factors. So far, hundreds of genome-wide significant single nucleotide polymorphisms (SNPs) associated with handgrip strength, lean mass and walking pace have been identified in the UK Biobank cohort; however, their pleiotropic effects on all three phenotypes have not been investigated. By combining summary statistics of genome-wide association studies (GWAS) of handgrip strength, lean mass and walking pace, we have identified 78 independent SNPs (from 73 loci) associated with all three traits with consistent effect directions. Of the 78 SNPs, 55 polymorphisms were also associated with body fat percentage and 25 polymorphisms with type 2 diabetes (T2D), indicating that sarcopenia, obesity and T2D share many common risk alleles. Follow-up bioinformatic analysis revealed that sarcopenia risk alleles were associated with tiredness, falls in the last year, neuroticism, alcohol intake frequency, smoking, time spent watching television, higher salt, white bread, and processed meat intake; whereas protective alleles were positively associated with bone mineral density, serum testosterone, IGF1, and 25-hydroxyvitamin D levels, height, intelligence, cognitive performance, educational attainment, income, physical activity, ground coffee drinking and healthier diet (muesli, cereal, wholemeal or wholegrain bread, potassium, magnesium, cheese, oily fish, protein, water, fruit, and vegetable intake). Furthermore, the literature data suggest that single-bout resistance exercise may induce significant changes in the expression of 26 of the 73 implicated genes in m. vastus lateralis, which may partly explain beneficial effects of strength training in the prevention and treatment of sarcopenia. In conclusion, we have identified and characterized 78 SNPs associated with sarcopenia and 55 SNPs with sarcopenic obesity in European-ancestry individuals from the UK Biobank.

Biallelic mutations in the high-temperature requirement A serine peptidase 1 (HTRA1) gene are known to cause an extremely rare cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), which belongs to the group of hereditary cerebral small vessel diseases and is mainly observed in the Japanese population. Even though this pathology is inherited in an autosomal recessive manner, recent studies have described symptomatic carriers with heterozygous HTRA1 mutations who have milder symptoms than patients with biallelic HTRA1 mutations. We present the case of a Lithuanian male patient who had a stroke at the age of 36, experienced several transient ischemic attacks, and developed an early onset, progressing dementia. These clinical symptoms were associated with extensive leukoencephalopathy, lacunar infarcts, and microbleeds based on brain magnetic resonance imaging (MRI). A novel heterozygous in-frame HTRA1 gene deletion (NM_002775.5:c.533_535del; NP_002766.1:p.(Lys178del)) was identified by next generation sequencing. The variant was consistent with the patient’s phenotype, which could not be explained by alternative causes, appeared highly deleterious after in silico analysis, and was not reported in the medical literature or population databases to date.

The MSTN gene is a negative regulator of muscle growth that is attracting attention as a candidate gene for physical performance traits. We hypothesised that variants of MSTN might be associated with the status of elite athlete. We therefore sought to study the potential role of MSTN in the physical performance of athletes by analysing the whole coding sequence of the MSTN gene in a cohort of Lithuanian elite athletes (n = 103) and non-athletes (n = 127). Consequently, two genetic variants were identified: the deletion of one of three adenines in the first intron (c.373+90delA, rs11333758) and a non-synonymous variant in the second exon (c.458A&gt, G, p.Lys(K)153Arg(R), rs1805086). Among all samples, the MSTN rs1805086 Lys(K) allele was the most common form in both groups. Homozygous genotype for the less common Arg(R) allele was identified in only one elite canoe rower, and we could find no direct association between rs1805086 and successful results in elite athletes. Surprisingly, the intronic variant (rs11333758) was abundant among all samples. The main finding was that endurance-oriented athletes had 2.1 greater odds of being MSTN deletion genotype than non-athletes (13.6% vs. 0.8%). The present study confirms the association of the polymorphism rs11333758 with endurance performance status in Lithuanian elite athletes.

The prehistory of the Lithuanian population and genetic relationship to other populations are poorly studied. Thus, the Lithuanian population, as an object of study, is interesting due to its partial isolation with genetic distinctiveness within the European context and with preserved ancient genetic composition. The main objects of this study was to infer demographic parameters, effective population size (Ne), and divergence time using high-density single nucleotide polymorphism (SNP) genotyping data generated with the Illumina HumanOmmiExpress-12v1.1 array in 295 individuals from the Lithuanian population and to compare our data with other populations from the Human Genome Cell Line Diversity Panel (HGDP-CEPH). We also aimed to reconstruct past events between the main ethnolinguistic regions&mdash, Auk&scaron, taitija and Žemaitija of Lithuania. Historically, these regions probably developed as two independent Baltic tribes. Our results of Ne in the Lithuanian population through time demonstrated a substantial reduction of Ne over the 150,000&ndash, 25,000 years before present (YBP). The estimated long-term Ne of the Lithuanian population is quite low&mdash, it equals 5404, which likely is a consequence of the bottlenecks associated with the last glacial period of 25,000&ndash, 12,000 YBP in Europe. The obtained divergence time estimates between the study populations are in agreement with recent studies. The reconstructed past events in Auk&scaron, taitija and Žemaitija showed significant differences between these two regions of Lithuania.

Blepharophimosis is a fixed reduction in the vertical distance between the upper and lower eyelids with short palpebral fissures. It is a rare facial malformation and is considered an important diagnostic feature in dysmorphic analysis. It is likely that many patients with blepharophimosis-mental retardation syndrome have submicroscopic chromosomal rearrangements, and the use of molecular karyotyping can narrow the known blepharophimosis-mental retardation-critical regions or clarify the effect of the haploinsufficiency of the involved genes on the phenotype.A female patient presented with bilateral blepharophimosis, ptosis, epicanthus inversus, telecanthus, low-set and small ears, other minor anomalies, hypotonia and psychomotor developmental delay. Metabolic investigations and array CGH analysis were performed. The results of molecular karyotyping were confirmed by real-time PCR analysis.Molecular karyotyping revealed a 5.2 Mb deletion in the 10q22.1q22.3 region. Real-time PCR analysis of the proband and her parents confirmed the deletion in the proband and revealed its de novo origin.With ptosis, hypotonia, and developmental delay as the main diagnostic features of our patient, the effect of histone acetyltransferase-encoding KAT6B gene haploinsufficiency was suspected to have a significant role in determining the phenotype. Detailed clinical characterization of the patient provided additional information on the clinical manifestation of the 10q22 deletion.

Molecular biologists and medical geneticists have to analyze large lists of genes and genomic variants to select the best candidates linked to the phenotype of interest. This task is very challenging therefore computational algorithms are used to prioritize candidate genes. Genes are prioritized based on evidence in favour of their relationship to the phenotype. A technique among other used in this process is measuring semantic similarity (SS) between functional annotations of genes. For SS to be applicable the functional annotations (knowledge about the domain) have to be in a form of hierarchically organized ontology. In this article we outline a computational process of estimating semantic similarity of phenotypic descriptions and gene annotations in Human Phenotype Ontology (HPO) and Gene Ontology. An example of a possible process of differential diagnosis applying semantic similarity to compare HPO phenotypes is presented. A semantic content of Gene Ontology annotations is highlighted. An example of comparison of meanings of individual GO annotations is presented and extended to a comparison of functional similarity of gene products.

ACE (I/D), ACTN3 (R/X), PPARGC1A (Gly482Ser) and PPARA (G/C) polymorphisms have been linked to the success in power-oriented sports through the intermediate phenotypes. The study involved 193 Lithuanian elite athletes and 250 controls. The measured phenotypic variables included short-term explosive muscle power (STEMP) and anaerobic alactic maximum power (AAMP). ACE DD genotype was more common among endurance athletes compared to the power athletes. The ACTN3 genotype frequencies of the elite athletes differed from those of non-elite athletes; however, there were no differences among the athletes and the control group across the PPARGC1A Gly482Ser genotypes. The frequency of PPARA CC genotype increased with the growing skill level of athletes (non-elite 2%, sub-elite 7.7%, elite 11.6%). The STEMP and AAMP were higher in the males than females and they were also higher in the power-oriented group compared to the endurance sports group. Success in power sports can be attributed to the ACE II, PPARGC1A SerSer, PPARA CC genotype in association with phenotypic characteristics such as AAMP and STEMP. ACTN3 XX genotype may not be critical but rather additive to endurance performance. The results show that high muscle power depends on both environmental and genetic factors.

Background. We aim to link fitness-related genotypes to the development of specific physical fitness phenotypes and a predisposition towards a specific sport category in Lithuanian elite athletes. Materials and methods. The study involved 193 athletes (152 male and 41 female) and 250 controls. The athletes were stratified into four groups: endurance, mixed sports, speed / power, and team sports. Genotypes of the athletes were identified according to the genetic polymorphisms: ACE (rs1799752), ACTN3 (rs1815739), PPARGC1A (rs8192678) and PPARA (rs4253778). One-way analysis of variance and logistic regression modelling were used for testing the genotype–phenotype association. Results. The frequency of ACE I allele was higher in athletes than in controls, although only male athletes showed a significant difference from male controls. The PPARA C allele was more common in the athlete group than in the general population of Lithuania. There were no significant ACTN3 and PPARGC1A SNP allele / genotype frequency differences between the athlete group and the controls. We have found that the ACTN3 RR genotype is associated with single muscular contraction power; the PPARGC1A Ser482Ser was associated with the muscle fat mass index; the PPARA CC and ACE II genotypes are associated with the muscle mass and single muscular contraction power. The effect of the gene variants was different for male and female athletes. Conclusions. The ACE II, PPARA CC, ACTN3 RR genotypes are related to the speed/power sports and the ACE DD, PPARA GG are related to the endurance sports in Lithuanian athletes. PPARGC1A Ser482Ser may be not critical but rather additive to endurance performance. Keywords: physical performance, ACE, ACTN3, PPARGC1A and PPARA genetic variants, sport category

Human athletic performance is a complex phenotype influenced by environmental and genetic factors, with most exercise-related traits being polygenic in nature. The aim of this article is to outline some of the challenge faced by sports genetics as this relatively new field moves forward. This review summarizes recent advances in sports science and discusses the impact of the genome, epigenome and other omics (such as proteomics and metabolomics) on athletic performance. The article also highlights the current status of gene doping and examines the possibility of applying genetic knowledge to predict athletes’ injury risk and to prevent the rare but alarming occurrence of sudden deaths during sporting events. Future research in large cohorts of athletes has the potential to detect new genetic variants and to confirm the previously identified DNA variants believed to explain the natural predisposition of some individuals to certain athletic abilities and health benefits. It is hoped that this article will be useful to sports scientists who seek a greater understanding of how genetics influences exercise science and how genomic and other multi-omics approaches might support performance analysis, coaching, personalizing nutrition, rehabilitation and sports medicine, as well as the potential to develop new rationale for future scientific investigation.