Admixed populations arise when two or more ancestral populations interbreed. As a result of this admixture, the genome of admixed populations is defined by tracts of variable size inherited from ...these parental groups and has particular genetic features that provide valuable information about their demographic history. Diverse methods can be used to derive the ancestry apportionment of admixed individuals, and such inferences can be leveraged for the discovery of genetic loci associated with diseases and traits, therefore having important biomedical implications. In this review article, we summarize the most common methods of global and local genetic ancestry estimation and discuss the use of admixture mapping studies in human diseases.
Despite asthma has a considerable genetic component, an important proportion of genetic risks remain unknown, especially for non-European populations. Canary Islanders have the largest African ...genetic ancestry observed among Southwestern Europeans and the highest asthma prevalence in Spain. Here we examined broad chromosomal regions previously associated with an excess of African genetic ancestry in Canary Islanders, with the aim of identifying novel risk variants associated with asthma susceptibility. In a two-stage cases-control study, we revealed a variant within HLA-DQB1 significantly associated with asthma risk (rs1049213, meta-analysis p = 1.30 × 10
, OR 95% CI = 1.74 1.41-2.13) previously associated with asthma and broad allergic phenotype. Subsequent fine-mapping analyses of classical HLA alleles revealed a novel allele significantly associated with asthma protection (HLA-DQA1*01:02, meta-analysis p = 3.98 × 10
, OR 95% CI = 0.64 0.50-0.82) that had been linked to infectious and autoimmune diseases, and peanut allergy. HLA haplotype analyses revealed a novel haplotype DQA1*01:02-DQB1*06:04 conferring asthma protection (meta-analysis p = 4.71 × 10
, OR 95% CI = 0.47 0.29- 0.73).
Resistin is a cytokine related with inflammation and ischemic heart disease. Physical activity (PA) prevents chronic inflammation and ischemic heart disease. We studied the relationship of serum ...concentration of resistin with HDL cholesterol, a known biomarker of PA, and with different measures of PA, in a large sample of the general adult population in the Canary Islands.
Cross-sectional study of 6636 adults recruited randomly. We analyzed the correlation of resistin and HDL cholesterol with PA (as metabolic equivalent level MET), and fitted the results with linear and logistic regression models using adjustment for age, alcohol consumption and smoking.
Mean resistin level was higher in women (p<0.001), correlated inversely with age, HDL cholesterol (p<0.001) and alcohol consumption (p<0.001 in men), and correlated directly with smoking (p<0.001). Resistin correlated inversely with the duration of leisure time PA (p<0.001), leisure time MET (p<0.001) and moderate leisure time PA (p<0.001), with some differences between sexes. Men (OR = 0.78 0.61-0.99; p<0.05) and women (OR = 0.75 0.61-0.92; p<0.01) in the upper quintile of leisure time PA had a lower risk of elevated resistin. In contrast, a high degree of sedentarism was associated with an increased risk elevated resistin in women (OR = 1.24 1.04-1.47; p<0.05 and in men (OR = 1.40 1.01-1.82; p<0.05).
In our sample of the general population, resistin was inversely associated with measures and levels of PA and HDL cholesterol. The association of resistin with PA was stronger than the association of HDL cholesterol with PA, making resistin a potentially useful biomarker of PA.
To analyze the trend of lower extremity major amputations (MA) among patients with type 2 diabetes mellitus (T2DM) in the Regions of Spain from year 2001 until 2015.
Descriptive study of 40,392 MA. ...Data were obtained from the national hospital discharge database in patients with T2DM. The incidence rate was calculated in each Region, in addition to the incidence ratios (IR) between annual incidence and incidence of the year 2001. The length of hospital stay and mortality risks were analyzed using regression models adjusted for sex, age and smoking.
The major amputations incidence rate per 100,000 person-years was 0.48 in Spain; Canary Islands showed the highest incidence (0.81). The trend was a slight decrease or stability of the incidence in all Regions except in the Canary Islands (IR
= 2.0 CI95% = 1.5, 2.6) and in Madrid (IR
= 0.1 CI95% = 0.1, 0.2). Mortality after major amputations was 10% in Spain; Cantabria suffered the highest risk of death 1.7 (CI95% = 1.4; 2.1), p < 0.001 and La Rioja the lowest risk (0.5 CI95% = 0.2; 0.9; p = 0.026). The longest hospital stay was registered in the Canary Islands (CI95% = 11.4;13.3, p < 0.001), and the shortest in the Valencian Community (CI95% = - 7.3; - 5.8), p < 0.001).
MA in T2DM followed a growing trend in the Canary Islands, which diverged from the downward trend in Spain. The variability of mortality and hospital stay, suggest to review the clinical management in some Regions. Sudden incidence decrease in Madrid suggests checking the record procedures of hospital discharges.
To determine whether the risk of cardiovascular mortality associated with cardiorenal syndrome subtype 1 (CRS1) in patients who were hospitalized for acute coronary syndrome (ACS) was greater than ...the expected risk based on the sum of its components, to estimate the predictive value of CRS1, and to determine whether the severity of CRS1 worsens the prognosis.
Follow-up study of 1912 incident cases of ACS for 1 year after discharge. Cox regression models were estimated with time to event (in-hospital death, and readmission or death during the first year after discharge) as the dependent variable.
The incidence of CRS1 was 9.2/1000 person-days of hospitalization (95% CI = 8.1-10.5), but these patients accounted for 56.6% (95% CI = 47.4-65.) of all mortality. The positive predictive value of CRS1 was 29.6% (95% CI = 23.9-36.0) for in-hospital death, and 51.4% (95% CI = 44.8-58.0) for readmission or death after discharge. The risk of in-hospital death from CRS1 (RR = 18.3; 95% CI = 6.3-53.2) was greater than the sum of risks associated with either acute heart failure (RR = 7.6; 95% CI = 1.8-31.8) or acute kidney injury (RR = 2.8; 95% CI = 0.9-8.8). The risk of events associated with CRS1 also increased with syndrome severity, reaching a RR of 10.6 (95% CI = 6.2-18.1) for in-hospital death at the highest severity level.
The effect of CRS1 on in-hospital mortality is greater than the sum of the effects associated with each of its components, and it increases with the severity of the syndrome. CRS1 accounted for more than half of all mortality, and its positive predictive value approached 30% in-hospital and 50% after discharge.
Abstract
The current inhabitants of the Canary Islands have a unique genetic makeup in the European diversity landscape due to the existence of African footprints from recent admixture events, ...especially of North African components (> 20%). The underrepresentation of non-Europeans in genetic studies and the sizable North African ancestry, which is nearly absent from all existing catalogs of worldwide genetic diversity, justify the need to develop CIRdb, a population-specific reference catalog of natural genetic variation in the Canary Islanders. Based on array genotyping of the selected unrelated donors and comparisons against available datasets from European, sub-Saharan, and North African populations, we illustrate the intermediate genetic differentiation of Canary Islanders between Europeans and North Africans and the existence of within-population differences that are likely driven by genetic isolation. Here we describe the overall design and the methods that are being implemented to further develop CIRdb. This resource will help to strengthen the implementation of Precision Medicine in this population by contributing to increase the diversity in genetic studies. Among others, this will translate into improved ability to fine map disease genes and simplify the identification of causal variants and estimate the prevalence of unattended Mendelian diseases.
Acute respiratory distress syndrome (ARDS) is an inflammatory process of the lungs that develops primarily in response to pulmonary or systemic sepsis, resulting in a disproportionate death toll in ...intensive care units (ICUs). Given its role as a critical activator of the inflammatory and innate immune responses, previous studies have reported that an increase of circulating cell-free mitochondrial DNA (mtDNA) is a biomarker for fatal outcome in the ICU. Here we analyzed the association of whole-blood mtDNA (wb-mtDNA) copies with 28-day survival from sepsis and sepsis-associated ARDS. We analyzed mtDNA data from 687 peripheral whole-blood samples within 24 h of sepsis diagnosis from unrelated Spanish patients with sepsis (264 with ARDS) included in the GEN-SEP study. The wb-mtDNA copies were obtained from the array intensities of selected probes, with 100% identity with mtDNA and with the largest number of mismatches with the nuclear sequences, and normalized across the individual-probe intensities. We used Cox regression models for testing the association with 28-day survival. We observed that wb-mtDNA copies were significantly associated with 28-day survival in ARDS patients (hazard ratio = 3.65, 95% confidence interval = 1.39-9.59, p = 0.009) but not in non-ARDS patients. Our findings support that wb-mtDNA copies at sepsis diagnosis could be considered an early prognostic biomarker in sepsis-associated ARDS patients. Future studies will be needed to evaluate the mechanistic links of this observation with the pathogenesis of ARDS.
Irisin is a myokine with a potential role in cardiometabolic diseases, but previous studies have described inconsistencies between serum irisin and physical activity (PA). Our aim was to analyze the ...relationship between serum irisin and leisure-time PA (LTPA) in a large sample of the general adult population, and secondarily, to evaluate its relationship with two PA-related biomarkers (HDL cholesterol and resistin).
A cross-sectional study was nested in the “CDC of the Canary Islands” cohort participants (n = 3827, 18–75 years, 60% women). PA was collected by administering the Minnesota leisure-time physical activity questionnaire, and physical examination and blood tests (irisin, resistin, HDL-cholesterol) were performed.
Irisin inversely correlated with BMI (p < 0.001 in women) and resistin (p = 0.038 in women, p = 0.004 in men), and directly with HDL cholesterol (p < 0.001in women). There was a direct association of irisin with leisure-time and energy expenditure in light, moderate and vigorous LTPA, which was stronger in women than men. The distribution of leisure-time and PA variables across irisin quintiles showed a significant trend, except for light LPTA in men. Adjusting for age, sex and BMI, the association of irisin with leisure-time and LTPA variables was stronger than the association of these variables with resistin and HDL cholesterol, reaching the strongest association for irisin with the 80th percentile of time of LTPA (OR = 2.57; 95% CI = 2.00–3.31).
There is a direct and independent association between serum irisin levels and LTPA in the general adult population, which is stronger than other biomarkers of PA. Findings on exercise-related irisin support the possibility of irisin health benefits.
Whole-exome sequencing has become a popular technique in research and clinical settings, assisting in disease diagnosis and increasing the understanding of disease pathogenesis. In this study, we ...aimed to compare common enrichment capture solutions available in the market. Peripheral blood-purified DNA samples were enriched with SureSelectQXT V6 (Agilent) and various Illumina solutions: TruSeq DNA Nano, TruSeq DNA Exome, Nextera DNA Exome, and Illumina DNA Prep with Enrichment, and sequenced on a HiSeq 4000. We found that their percentage of duplicate reads was as much as 2 times higher than previously reported values for the previous HiSeq series. SureSelectQXT and Illumina DNA Prep with Enrichment showed the best average on-target coverage, which improved when off-target regions were included. At high coverage levels and in shared bases, these two solutions and TruSeq DNA Exome provided three of the best performances. With respect to the number of small variants detected, SureSelectQXT presented the lowest number of detected variants in target regions. When off-target regions were considered, its ability equalized to other solutions. Our results show SureSelectQXT and Illumina DNA Prep with Enrichment to be the best enrichment capture solutions.
Highlights • DIABSCORE was developed and validated an risk score for screening of type 2 diabetes in a general population cohort. • DIABSCORE showed a high sensitivity to detect cases of type 2 ...diabetes and a high negative predictive value to rule out the presence of diabetes. • DIABSCORE has showed to be a valid method for opportunistic screening of type 2 diabetes in primary care that is applicable in different populations. • DIABSCORE does not require invasive methods and competes advantageously with blood glucose and HbA1c in terms of patient and professional satisfaction. • DIABSCORE is a cost-effective screening method for type 2 diabetes in primary care compared to the use of blood glucose or HbA1c.
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