A genome-wide association study of adults with community-acquired pneumonia.

Background: Community-acquired pneumonia (CAP) is associated with high morbidity and hospitalization rate. In infectious diseases, host genetics plays a critical role in susceptibility and immune response, and the immune pathways involved are highly dependent on the microorganism and its route of infection. Here we aimed to identify genetic risk loci for CAP using a case-control genome-wide association study (GWAS).

Does HLA explain the high incidence of childhood-onset type 1 diabetes in the Canary Islands? The role of Asp57 DQB1 molecules.

Unlabelled: The Canary Islands inhabitants, a recently admixed population with significant North African genetic influence, has the highest incidence of childhood-onset type 1 diabetes (T1D) in Spain and one of the highest in Europe. HLA accounts for half of the genetic risk of T1D.

Aims: To characterize the classical HLA-DRB1 and HLA-DQB1 alleles in children from Gran Canaria with and without T1D.

Irisin, in women and men: blood pressure, heart rate, obesity and insulin resistance.

Background: Irisin is a myokine that increases with leisure time physical activity (LTPA) and for which a cardiovascular protective role has been postulated. Our aim was to assess this role in the general population.

Methods: A cross-sectional analysis was performed in a large randomly selected population sample (n=2298 women and 1529 men).

Resistin as a risk factor for all-cause (and cardiovascular) death in the general population.

Serum resistin is a pro-inflammatory cytokine that has been described as a risk factor associated with mortality in several clinical sets including type 2 diabetes. Mortality studies in the general population are needed to find out the risk of death associated to this cytokine. In a follow-up study of a cohort of adult population (n = 6636) in Spain over a period of fifteen years (447 deaths/102,255 person-years), serum resistin measurements and death records were obtained.

Irisin is more strongly associated with leisure-time physical activity than resistin and high-density lipoprotein cholesterol are.

Obectives: 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).

Design: A cross-sectional study was nested in the "CDC of the Canary Islands" cohort participants (n = 3827, 18-75 years, 60% women).

A catalog of the genetic causes of hereditary angioedema in the Canary Islands (Spain).

Hereditary angioedema (HAE) is a rare disease where known causes involve C1 inhibitor dysfunction or dysregulation of the kinin cascade. The updated HAE management guidelines recommend performing genetic tests to reach a precise diagnosis. Unfortunately, genetic tests are still uncommon in the diagnosis routine.

Developing CIRdb as a catalog of natural genetic variation in the Canary Islanders.

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.

Evaluation of a whole-exome sequencing pipeline and benchmarking of causal germline variant prioritizers.

Most causal variants of Mendelian diseases are exonic. Whole-exome sequencing (WES) has become the diagnostic gold standard, but causative variant prioritization constitutes a bottleneck. Here we assessed an in-house sample-to-sequence pipeline and benchmarked free prioritization tools for germline causal variants from WES data.

Admixture Mapping of Sepsis in European Individuals With African Ancestries.

Sepsis is a severe systemic inflammatory response to infections that is accompanied by organ dysfunction. Although the ancestral genetic background is a relevant factor for sepsis susceptibility, there is a lack of studies using the genetic singularities of a recently admixed population to identify loci involved in sepsis susceptibility. Here we aimed to discover new sepsis loci by completing the first admixture mapping study of sepsis in Canary Islanders, leveraging their distinctive genetic makeup as a mixture of Europeans and African ancestries.

Incidence and mortality of cerebrovascular disease in Spain: 1,600,000 hospital admissions between 2001 and 2015.

Background: To analyze the incidence and mortality of cerebrovascular diseases (CeVD) in Spain from 2001 to 2015.

Methods: Retrospective study of hospital incidence, hospital case fatality and population mortality, with records from the Spanish Government Statistics. Days of hospital stay and risk of death (RD) during admission were estimated adjusting for age, sex, first stroke (FS), atrial fibrillation (AF), diabetes, hypertension, and smoking.

Targeted analysis of genomic regions enriched in African ancestry reveals novel classical HLA alleles associated with asthma in Southwestern Europeans.

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.

First Census of Patients with Hereditary Angioedema in the Canary Islands.

Hereditary angioedema (HAE) is a rare genetic condition whose main symptoms are recurrent swelling in the skin, mucosa, and internal organs. Recent studies suggested that the regulation of the inflammatory response and the complement cascade are two of the pathways significantly enriched in the Canary Islands, Spain. Here, we describe the first HAE patient series in this region.

Whole-Blood Mitochondrial DNA Copies Are Associated With the Prognosis of Acute Respiratory Distress Syndrome After Sepsis.

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.

Genetic Ancestry Inference and Its Application for the Genetic Mapping of Human Diseases.

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.

Evaluation of Whole-Exome Enrichment Solutions: Lessons from the High-End of the Short-Read Sequencing Scale.

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 SureSelect 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.

Interactive Web-Based Resource for Annotation of Genetic Variants Causing Hereditary Angioedema (HADA): Database Development, Implementation, and Validation.

Background: Hereditary angioedema is a rare genetic condition caused by C1 esterase inhibitor deficiency, dysfunction, or kinin cascade dysregulation, leading to an increased bradykinin plasma concentration. Hereditary angioedema is a poorly recognized clinical entity and is very often misdiagnosed as a histaminergic angioedema. Despite its genetic nature, first-line genetic screening is not integrated in routine diagnosis.

Corrigendum: Bradykinin-Mediated Angioedema: An Update of the Genetic Causes and the Impact of Genomics.

[This corrects the article DOI: 10.3389/fgene.2019.

Admixture mapping of asthma in southwestern Europeans with North African ancestry influences.

The prevalence of asthma symptoms in Canary Islanders, a southwestern European population from Spain, is almost three times higher than the country average. Because the genetic risks identified so far explain <5% of asthma heritability, here we aimed to discover new asthma loci by completing the first admixture mapping study in Canary Islanders leveraging their distinctive genetic makeup, where significant northwest African influences coexist in the European genetic diversity landscape. A 2-stage study was conducted in 1,491 unrelated individuals self-declaring having a Canary Islands origin for the 4 grandparents.

Major amputations in type 2 diabetes between 2001 and 2015 in Spain: regional differences.

Background: 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.

Methods: Descriptive study of 40,392 MA. Data were obtained from the national hospital discharge database in patients with T2DM.

Bradykinin-Mediated Angioedema: An Update of the Genetic Causes and the Impact of Genomics.

Recurrent episodes of bradykinin-mediated angioedema (Bk-AE) can associate with acquired or hereditary conditions, the former most commonly developing secondarily to a pharmacological treatment. Despite successful genomic advances that have led to the identification of a large number of disease genes irrespective of disease prevalence, their application to Bk-AE has barely occurred. As a consequence, the genetic causes of Bk-AE remain poorly understood, obstructing the identification of patient subtypes and the development of precision medicine strategies.

Domain and intensity of physical activity are associated with metabolic syndrome: A population-based study.

Introduction: Little is known on how the domain and intensity of physical activity (PA) associates with metabolic syndrome (MetS). The aim of this study was to examine associations between PA domains (leisure-time, domestic, active transport, total walking and total PA), PA intensities (light, moderate and vigorous) and PA levels with MetS in the general adult population.

Methods: Cross-sectional study.

Genomic Analyses of Human European Diversity at the Southwestern Edge: Isolation, African Influence and Disease Associations in the Canary Islands.

Despite the genetic resemblance of Canary Islanders to other southern European populations, their geographical isolation and the historical admixture of aborigines (from North Africa) with sub-Saharan Africans and Europeans have shaped a distinctive genetic makeup that likely affects disease susceptibility and health disparities. Based on single nucleotide polymorphism array data and whole genome sequencing (30×), we inferred that the last African admixture took place ∼14 generations ago and estimated that up to 34% of the Canary Islander genome is of recent African descent. The length of regions in homozygosis and the ancestry-related mosaic organization of the Canary Islander genome support the view that isolation has been strongest on the two smallest islands.

Hospital Mortality in 415 798 AMI Patients: 4 Years Earlier in the Canary Islands Than in the Rest of Spain.

Introduction And Objectives: The Canary Islands has the highest mortality from diabetes in Spain. The aim of this study was to determine possible differences in mortality due to acute myocardial infarction (AMI) during hospital admission between this autonomous community and the rest of Spain, as well as the factors associated with this mortality and the population fraction attributable to diabetes.

Methods: Cross-sectional study of hospital admissions for AMI in Spain from 2007 to 2014, registered in the Minimum Basic Data Set.

Austerity Policies and Mortality in Spain After the Financial Crisis of 2008.

Objectives: To analyze mortality in Spain and the United States before and after these countries implemented divergent policies in response to the financial crisis of 2008.

Methods: We examined mortality statistics in both countries in the years 2000 to 2015. Spain started austerity policies in 2010.