Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10⁻⁸) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10⁻²² and P = 8.1 × 10⁻¹², respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10⁻⁸). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10⁻⁸) and ARHGAP33 (P = 1.3 × 10⁻⁸), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10⁻⁸). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.

The genetic profile that is needed to identify talents has been studied extensively in recent years. The main objective of this investigation was to approach, for the first time, the study of genetic variants in several polygenic profiles and their role in elite endurance and professional football performance by comparing the allelic and genotypic frequencies to the non-athlete population. In this study, genotypic and allelic frequencies were determined in 452 subjects: 292 professional athletes (160 elite endurance athletes and 132 professional football players) and 160 non-athlete subjects. Genotyping of polymorphisms in liver metabolisers (CYP2D6, GSTM1, GSTP and GSTT), iron metabolism and energy efficiency (HFE, AMPD1 and PGC1a), cardiorespiratory fitness (ACE, NOS3, ADRA2A, ADRB2 and BDKRB2) and muscle injuries (ACE, ACTN3, AMPD1, CKM and MLCK) was performed by Polymerase Chain Reaction-Single Nucleotide Primer Extension (PCR-SNPE). The combination of the polymorphisms for the “optimal” polygenic profile was quantified using the genotype score (GS) and total genotype score (TGS). Statistical differences were found in the genetic distributions between professional athletes and the non-athlete population in liver metabolism, iron metabolism and energy efficiency, and muscle injuries (p<0.001). The binary logistic regression model showed a favourable OR (odds ratio) of being a professional athlete against a non-athlete in liver metabolism (OR: 1.96; 95% CI: 1.28–3.01; p = 0.002), iron metabolism and energy efficiency (OR: 2.21; 95% CI: 1.42–3.43; p < 0.001), and muscle injuries (OR: 2.70; 95% CI: 1.75–4.16; p < 0.001) in the polymorphisms studied. Genetic distribution in professional athletes as regards endurance (professional cyclists and elite runners) and professional football players shows genetic selection in these sports disciplines.

Many causes define injuries in professional soccer players. In recent years, the study of genetics in association with injuries has been of great interest. The purpose of this study was to examine the relationship between muscle injury-related genes, injury risk and injury etiology in professional soccer players. In a cross-sectional cohort study, one hundred and twenty-two male professional football players were recruited. AMPD1 (rs17602729), ACE (rs4646994), ACTN3 (rs1815739), CKM (rs8111989) and MLCK (rs2849757 and rs2700352) polymorphisms were genotyped by using Single Nucleotide Primer Extension (SNPE). The combined influence of the six polymorphisms studied was calculated using a total genotype score (TGS). A genotype score (GS) of 2 was assigned to the “protective” genotype for injuries, a GS of 1 was assigned to the heterozygous genotype while a GS of 0 was assigned to the “worst” genotype. Injury characteristics and etiology during the 2021/2022 season were classified following a Consensus Statement for injuries recording. The distribution of allelic frequencies in the AMPD1 and MLCK c.37885C>A polymorphisms were different between non-injured and injured soccer players (p < 0.001 and p = 0.003, respectively). The mean total genotype score (TGS) in non-injured soccer players (57.18 ± 14.43 arbitrary units [a.u.]) was different from that of injured soccer players (51.71 ± 12.82 a.u., p = 0.034). There was a TGS cut-off point (45.83 a.u.) to discriminate non-injured from injured soccer players. Players with a TGS beyond this cut-off had an odds ratio of 1.91 (95%CI: 1.14–2.91; p = 0.022) to suffer an injury when compared with players with lower TGS. In conclusion, TGS analysis in muscle injury-related genes presented a relationship with professional soccer players at increased risk of injury. Future studies will help to develop this TGS as a potential tool to predict injury risk and perform prevention methodology in this cohort of football players.

Diamine oxidase (DAO) is an enzyme that metabolizes intestinal histamine. Single nucleotide polymorphisms (SNPs) of the Amine Oxidase Copper Containing 1 (AOC1) gene can lead to low enzymatic activity or functionality in histamine metabolism. This study aimed to determine the prevalence of DAO deficiency for four variants of the AOC1 gene, p.Thr16Met (rs10156191), p.Ser332Phe (rs1049742), p.His664Asp (rs1049793), and c.691G > T (rs2052129), in 98 Spanish women with fibromyalgia between the ages of 33 and 60 years, and compare the distribution of allelic and genotypic frequencies with those of European population samples in Hardy–Weinberg equilibrium extracted from the Allele Frequency Aggregator (ALFA) database. The patients’ DNA was extracted, and analyzed using SNPE Multiplex (Single Nucleotide Primer Extension). The prevalence of genetic DAO deficiency was 74.5% based on the four variants of the AOC1 gene. SNP deficits were found at frequencies of 53.1% for p.Thr16Met, 49% for c.691G > T, 48% for p.His664Asp, and 19.4% for p.Ser332Phe. The allele and genotypic frequencies of the women with fibromyalgia did not differ from the European population. Variants of the AOC1 gene that are associated with genetic DAO deficiency could serve as a disruptive biomarker in patients with fibromyalgia. This study was registered in ClinicalTrials.gov Identifier: NCT05389761.

This work was directed to evaluate immunoexpression of markers for apoptosis, resistance to apoptosis, and cell proliferation, as well as estimates of nuclear size in ventral prostate of rats treated with cadmium chloride and cadmium + zinc chloride because a possible protective effect of zinc has been postulated. The following variables were studied: volume fraction (V_F) of Bcl-2 immunostaining, percentage of cells immunoreactive to proliferating cell nuclear antigen (LI_PCNA) and p53 (LI_p53), numerical density of caspase-3 immunoreactive cells (N_Vcaspase-3), and estimates of volume-weighted mean nuclear volume (υ_V). The LI_PCNAand V_Fof Bcl-2 were significantly increased in the treated animals. The dysplasias (independent of their origin) showed a significant increase of the LI_p53, N_Vcaspase-3, and υ_Vin comparison with normal acini from treated and control animals. It can be concluded that cell proliferation is enhanced in long-term cadmium-exposed rats, and exposure to zinc combined with cadmium had no effect on any of the variables studied when comparing with normal acini. The increase of nuclear υ_Vcould indicate a more aggressive behavior for pretumoral lesions.

The influence of the rs8111989 polymorphism in the muscle-specific creatine kinase gene (CKM) on injury incidence is unknown. The aim was to investigate CKM polymorphism on injury incidence in high-performance football players. A cohort of 109 high-performance players was genotyped by using saliva samples. Injury incidence was similar in players with the GG, GA, and AA genotypes and did not modify incidence during training or match exposure (p=0.583 and p=0.737 respectively). GG players had a higher frequency of slight-severity injuries (60.0 vs. 10.2 vs. 24.2%, p<0.001), while GA players had a higher frequency of severe injuries (16.7 vs. 30.8 vs. 10.0%, p=0.021). GA players also had a higher frequency of muscle tears (34.8 vs. 59.0 vs. 20.0%, p<0.001). Muscle contracture was a more frequent injury in players with the GG genotype (40.0%, p<0.001). G allele carriers had lower frequencies of gradual-onset injuries (4.1 vs. 16.7%, p=0.035) and recurrent injuries (6.1 vs. 16.7%, p=0.003) than AA players. A allele carriers had higher frequency of severe injuries (10.0 vs. 21.9%, p=0.044) than GG players. Genotypes in the CKM rs8111989 polymorphism did not affect injury incidence in high-performance football players. Players with the GA genotype were more prone to severe injuries and muscle tears when compared to GG and AA players.