Genomic inbreeding estimation, runs of homozygosity, and heterozygosity-enriched regions uncover signals of selection in the Quarter Horse racing line.

With the advent of genomics, significant progress has been made in the genetic improvement of livestock species, particularly through increased accuracy in predicting breeding values for selecting superior animals and the possibility of performing a high-resolution genetic scan throughout the genome of an individual. The main objectives of this study were to estimate the individual genomic inbreeding coefficient based on runs of homozygosity (FROH ), to identify and characterize runs of homozygosity and heterozygosity (ROH and ROHet, respectively; length and distribution) throughout the genome, and to map selection signatures in relevant chromosomal regions in the Quarter Horse racing line. A total of 336 animals registered with the Brazilian Association of Quarter Horse Breeders (ABQM) were genotyped. One hundred and twelve animals were genotyped using the Equine SNP50 BeadChip (Illumina, USA), with 54,602 single nucleotide polymorphisms (SNPs; 54K). The remaining 224 samples were genotyped using the Equine SNP70 BeadChip (Illumina, USA) with 65,157 SNPs (65K). To ensure data quality, we excluded animals with a call rate below 0.9. We also excluded SNPs located on non-autosomal chromosomes, as well as those with a call rate below 0.9 or a p-value below 1 × 10-5 for Hardy-Weinberg equilibrium. The results indicate moderate to high genomic inbreeding, with 46,594 ROH and 16,101 ROHet detected. In total, 30 and 14 candidate genes overlap with ROH and ROHet regions, respectively. The ROH islands showed genes linked to crucial biological processes, such as cell differentiation (CTBP1, WNT5B, and TMEM120B), regulation of glucose metabolic process (MAEA and NKX1-1), heme transport (PGRMC2), and negative regulation of calcium ion import (VDAC1). In ROHet, the islands showed genes related to respiratory capacity (OR7D19, OR7D4G, OR7D4E, and OR7D4J) and muscle repair (EGFR and BCL9). These findings could aid in selecting animals with greater regenerative capacity and developing treatments for muscle disorders in the QH breed. This study serves as a foundation for future research on equine breeds. It can contribute to developing reproductive strategies in animal breeding programs to improve and preserve the Quarter Horse breed.

Chagas disease is an independent predictor of stroke and death in a cohort of heart failure patients.

BACKGROUND AND AIMS: Chagas disease is a common cause of heart failure (HF) and death in developing countries. Although stroke is known to occur in these patients, an accurate estimate of stroke incidence is lacking. We aimed to determine the incidence of stroke and death in patients with HF, comparing Chagas and non-Chagas etiologies. METHODS: Cohort of stroke-free patients with HF (Framingham criteria) followed in a university-based outpatient clinic in Brazil. Baseline characteristics included sociodemographic, risk factor assessment, echocardiographic and electrocardiographic findings. Chagas disease was defined by appropriate serologic tests. Cause-specific Cox regression was used to search for predictors of stroke or death as separate outcomes. RESULTS: We studied 565 patients with HF between January 2003 and December 2018, mean age 54.3 ± 12.9 years, 305 (54.0%) females, 271/535 (50.7%) with Chagas disease. Chagas patients were older (55.5 vs. 53.1 years), more frequently women (60.5% vs. 47.3%), less frequently harbored coronary artery disease (14.5% vs. 34.1%) when compared to non-Chagas patients. Echocardiography showed more severe disease among non-Chagas patients [median left ventricle ejection fraction (LVEF) 37.3% vs. 47.0%]. Over a mean 42.9 (±34.4) months, we followed 404 (71.5%) patients, completing 1442 patient-years of follow-up. Stroke incidence was higher in Chagas when compared to non-Chagas patients (20.2 vs. 13.9 events per 1000 patient-years), while death rate was similar (41.6 vs. 43.1 deaths per 1000 patient-years). In the multivariable analysis for stroke outcome adjusted for LVEF and arrhythmias, cause-specific hazard ratio (CSHR) for Chagas was 2.54 (95% confidence interval 1.01-6.42, p = 0.048). Chagas disease was also associated with increased risk of death (CSHR 1.83; 95% confidence interval 1.04-3.24, p = 0.037). CONCLUSION: Chagas disease is associated with increased risk of stroke and death when compared to other etiologies of HF, independently of HF severity or cardiac arrhythmias, suggesting other factors contribute to increased stroke risk and mortality in Chagas disease. Early prevention and treatment of Chagas disease is imperative to reduce a later risk of stroke in endemic areas.

Association Between Risk of Obstructive Sleep Apnea and Cerebrovascular Reactivity in Stroke Patients.

Background Obstructive sleep apnea (OSA) is present in 60% to 70% of stroke patients. Cerebral vasoreactivity in patients with stroke and OSA has not been well studied and could identify a new pathophysiologic mechanism with potential therapeutic intervention. We aimed to determine whether risk categories for OSA are associated with cerebral vasoreactivity in stroke patients. Methods and Results In this cross-sectional study of a cohort of patients with stroke, we used clinical questionnaires (Sleep Obstructive Apnea Score Optimized for Stroke [SOS] and snoring, tiredness, observed, pressure, bmi, age, neck, gender [STOP-BANG] scores) to assess the risk of OSA and transcranial Doppler to assess cerebral vasoreactivity (breath-holding index and visual evoked flow velocity response). Of the 99 patients included, 77 (78%) had medium or high risk of OSA and 80 performed transcranial Doppler. Mean breath-holding index was 0.52±0.37, and median visual evoked flow velocity response was 10.8% (interquartile range: 8.8-14.5); 54 of 78 (69%) showed impaired anterior circulation vasoreactivity (breath-holding index <0.69) and 53 of 71 (75%) showed impaired posterior circulation vasoreactivity (visual evoked flow velocity response ≤14.0%). There was a significant negative correlation between the risk of OSA calculated by STOP-BANG and the breath-holding index (rS=-0.284, P=0.012). The following variables were associated with low anterior circulation vasoreactivity: dyslipidemia (odds ratio: 4.7; 95% CI, 1.5-14.2) and STOP-BANG score (odds ratio: 1.7 per 1-point increase; 95% CI, 1.1-1.5). Conclusions A high risk of OSA and impaired vasoreactivity exists in the population that has had stroke. Dyslipidemia and STOP-BANG sleep apnea risk categories were independently associated with impaired anterior circulation vasoreactivity.