Association of blood inflammatory phenotypes and asthma burden in children with moderate-to-severe asthma.

Background: Underlying immunological mechanisms in children with moderate-to-severe asthma are complex and unclear. We aimed to investigate the association between blood inflammatory parameters and asthma burden in children with moderate-to-severe asthma.

Methods: Blood inflammatory parameters (eosinophil and neutrophil counts and inflammatory mediators using multiplex immunoassay technology) were measured in children (6-17 years) with moderate-to-severe asthma from the SysPharmPediA cohort across four European countries.

Asthma-Genomic Advances Toward Risk Prediction.

Asthma is a common complex airway disease whose prediction of disease risk and most severe outcomes is crucial in clinical practice for adequate clinical management. This review discusses the latest findings in asthma genomics and current obstacles faced in moving forward to translational medicine. While genome-wide association studies have provided valuable insights into the genetic basis of asthma, there are challenges that must be addressed to improve disease prediction, such as the need for diverse representation, the functional characterization of genetic variants identified, variant selection for genetic testing, and refining prediction models using polygenic risk scores.

El Hierro Genome Study: A Genomic and Health Study in an Isolated Canary Island Population.

El Hierro is the smallest and westernmost island of the Canary Islands, whose population derives from an admixture of different ancestral components and that has been subjected to genetic isolation. We established the "El Hierro Genome Study" to characterize the health status and the genetic composition of ~10% of the current population of the island, accounting for a total of 1054 participants. Detailed demographic and clinical data and a blood sample for DNA extraction were obtained from each participant.

Precision medicine for asthma treatment: Unlocking the potential of the epigenome and microbiome.

Asthma is a leading worldwide biomedical concern. Patients can experience life-threatening worsening episodes (exacerbations) usually controlled by anti-inflammatory and bronchodilator drugs. However, substantial heterogeneity in treatment response exists, and a subset of patients with unresolved asthma carry the major burden of this disease.

Novel insights into the whole-blood DNA methylome of asthma in ethnically diverse children and youth.

Background: The epigenetic mechanisms of asthma remain largely understudied in African Americans and Hispanics/Latinos, two populations disproportionately affected by asthma. We aimed to identify markers, regions and processes with differential patterns of DNA methylation (DNAm) in whole blood by asthma status in ethnically diverse children and youth, and to assess their functional consequences.

Methods: DNAm levels were profiled with the Infinium MethylationEPIC or HumanMethylation450 BeadChip arrays among 1226 African Americans or Hispanics/Latinos and assessed for differential methylation per asthma status at the CpG and region (differentially methylated region (DMR)) level.

European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation.

Atopic dermatitis (AD) is a common inflammatory skin condition and prior genome-wide association studies (GWAS) have identified 71 associated loci. In the current study we conducted the largest AD GWAS to date (discovery N = 1,086,394, replication N = 3,604,027), combining previously reported cohorts with additional available data. We identified 81 loci (29 novel) in the European-only analysis (which all replicated in a separate European analysis) and 10 additional loci in the multi-ancestry analysis (3 novel).

Epigenomic response to albuterol treatment in asthma-relevant airway epithelial cells.

Background: Albuterol is the first-line asthma medication used in diverse populations. Although DNA methylation (DNAm) is an epigenetic mechanism involved in asthma and bronchodilator drug response (BDR), no study has assessed whether albuterol could induce changes in the airway epithelial methylome. We aimed to characterize albuterol-induced DNAm changes in airway epithelial cells, and assess potential functional consequences and the influence of genetic variation and asthma-related clinical variables.

The genomic history of the indigenous people of the Canary Islands.

The indigenous population of the Canary Islands, which colonized the archipelago around the 3 century CE, provides both a window into the past of North Africa and a unique model to explore the effects of insularity. We generate genome-wide data from 40 individuals from the seven islands, dated between the 3-16 centuries CE. Along with components already present in Moroccan Neolithic populations, the Canarian natives show signatures related to Bronze Age expansions in Eurasia and trans-Saharan migrations.

Alpha-1 antitrypsin deficiency and Pi*S and Pi*Z SERPINA1 variants are associated with asthma exacerbations.

Introduction And Objectives: Asthma is a chronic inflammatory disease of the airways. Asthma patients may experience potentially life-threatening episodic flare-ups, known as exacerbations, which may significantly contribute to the asthma burden. The Pi*S and Pi*Z variants of the SERPINA1 gene, which usually involve alpha-1 antitrypsin (AAT) deficiency, had previously been associated with asthma.

Multi-omic approach associates blood methylome with bronchodilator drug response in pediatric asthma.

Background: Albuterol is the drug most widely used as asthma treatment among African Americans despite having a lower bronchodilator drug response (BDR) than other populations. Although BDR is affected by gene and environmental factors, the influence of DNA methylation is unknown.

Objective: This study aimed to identify epigenetic markers in whole blood associated with BDR, study their functional consequences by multi-omic integration, and assess their clinical applicability in admixed populations with a high asthma burden.

Asthma Exacerbations: The Genes Behind the Scenes.

The clinical and socioeconomic burden of asthma exacerbations (AEs) constitutes a major public health problem. In the last 4 years, there has been an increase in ethnic diversity in candidate-gene and genome-wide association studies of AEs, which in the latter case led to the identification of novel genes and underlying pathobiological processes. Pharmacogenomics, admixture mapping analyses, and the combination of multiple "omics" layers have helped to prioritize genomic regions of interest and/or facilitated our understanding of the functional consequences of genetic variation.

The upper-airway microbiome as a biomarker of asthma exacerbations despite inhaled corticosteroid treatment.

Background: The response to inhaled corticosteroids (ICS) in asthma is affected by the interplay of several factors. Among these, the role of the upper-airway microbiome has been scarcely investigated. We aimed to evaluate the association between the salivary, pharyngeal, and nasal microbiome with asthma exacerbations despite receipt of ICS.

Admixture mapping of severe asthma exacerbations in Hispanic/Latino children and youth.

Background: In the USA, genetically admixed populations have the highest asthma prevalence and severe asthma exacerbations rates. This could be explained not only by environmental factors but also by genetic variants that exert ethnic-specific effects. However, no admixture mapping has been performed for severe asthma exacerbations.

Epigenome-wide association study of lung function in Latino children and youth with asthma.

Introduction: DNA methylation studies have associated methylation levels at different CpG sites or genomic regions with lung function. Moreover, genetic ancestry has been associated with lung function in Latinos. However, no epigenome-wide association study (EWAS) of lung function has been performed in this population.

Multiomics analysis identifies BIRC3 as a novel glucocorticoid response-associated gene.

Background: Inhaled corticosteroid (ICS) response among patients with asthma is influenced by genetics, but biologically actionable insights based on associations have not been found. Various glucocorticoid response omics data sets are available to interrogate their biological effects.

Objective: We sought to identify functionally relevant ICS-response genetic associations by integrating complementary multiomics data sets.

Role of Sex on the Genetic Susceptibility to Childhood Asthma in Latinos and African Americans.

Asthma is a respiratory disease whose prevalence changes throughout the lifespan and differs by sex, being more prevalent in males during childhood and in females after puberty. In this study, we assessed the influence of sex on the genetic susceptibility to childhood asthma in admixed populations. Sex-interaction and sex-stratified genome-wide association studies (GWAS) were performed in 4291 Latinos and 1730 African Americans separately, and results were meta-analyzed.