Genome‐wide association study reveals a novel locus for asthma with severe exacerbations in diverse populations

Herrera‐Luis, Esther; Espuela‐Ortiz, Antonio; Lorenzo-Díaz, Fabián; Keys, Kevin L.; Mak, Angel C. Y.; Eng, Celeste; Huntsman, Scott; Villar, Jesús; Rodríguez‐Santana, José; Burchard, Esteban G.; Pino-Yanes, María

doi:10.1111/pai.13337

Cited by 19 publications

(18 citation statements)

References 33 publications

(66 reference statements)

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“…The complete summary of the results is presented in Table S3. The asthma-associated variants in 2p21 near LDHAP3, a locus previously associated with severe asthma exacerbations in Latinos from GALA II [25], had a predominant effect in males and were nominally significant in the interaction and female-only analyses (p-value < 0.05) (Tables 3 and S3). However, variants upstream of LCORL at 4p15.31 had sex-specific involvement in male asthma susceptibility, being nominally significant in the interaction GWAS (p-value < 0.05), but not in females (p-value > 0.05) (Tables 3 and S3).…”

Section: Stratified Gwas In Femalesmentioning

confidence: 96%

“…Genotyping was carried out with the Axiom LAT1 array (817,810 genetic variants) and the Axiom LAT1 Array Plus HLA (812,715 SNPs) (Affymetrix), as described elsewhere [25], and joined quality control was carried out for the subset of 803,225 variants resulting from the intersection of the two arrays. Quality control main steps included the exclusion of individuals with: low call rate (<97%), a discrepancy between reported gender and biological sex, relatedness with other subjects (Pi-hat > 0.3), and evidence of being outliers for any of the three first principal components of the genotype matrix (>six standard deviations) estimated with PLINK 1.9 [47].…”

Section: Genotyping Imputation Of Genetic Variants and Ancestry Assessmentmentioning

confidence: 99%

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

Espuela‐Ortiz

Herrera‐Luis

Lorenzo-Díaz

et al. 2021

JPM

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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. Genome-wide (p ≤ 9.35 × 10−8) and suggestive (p ≤ 1.87 × 10−6) population-specific significance thresholds were calculated based on 1000 Genomes Project data. Additionally, protein quantitative trait locus (pQTL) information was gathered for the suggestively associated variants, and enrichment analyses of the proteins identified were carried out. Four independent loci showed interaction with sex at a suggestive level. The stratified GWAS highlighted the 17q12-21 asthma locus as a contributor to asthma susceptibility in both sexes but reached genome-wide significance only in females (p-females < 9.2 × 10−8; p-males < 1.25 × 10−2). Conversely, genetic variants upstream of ligand-dependent nuclear receptor corepressor-like gene (LCORL), previously involved in height determination and spermatogenesis, were associated with asthma only in males (minimum p = 5.31 × 10−8 for rs4593128). Enrichment analyses revealed an overrepresentation of processes related to the immune system and highlighted differences between sexes. In conclusion, we identified sex-specific polymorphisms that could contribute to the differences in the prevalence of childhood asthma between males and females.

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Section: Stratified Gwas In Femalesmentioning

confidence: 96%

Section: Genotyping Imputation Of Genetic Variants and Ancestry Assessmentmentioning

confidence: 99%

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

Espuela‐Ortiz

Herrera‐Luis

Lorenzo-Díaz

et al. 2021

JPM

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“…It is well known that genetics is a strong determinant for the risk of developing asthma exacerbations, particularly in persons with African ancestry. The second highlighted article by Esther Herrera‐Luis et al investigated this risk by genome‐wide association studies in various populations, including African Americans and Hispanics/Latino children with severe asthma exacerbations, as well as controls 9 . The initial screening included over 3000 individuals of various ethnic origins.…”

mentioning

confidence: 99%

“…The second highlighted article by Esther Herrera-Luis et al investigated this risk by genome-wide association studies in various populations, including African Americans and Hispanics/Latino children with severe asthma exacerbations, as well as controls. 9 The initial screening included over 3000 individuals of various ethnic origins. The study identified a novel genome-wide significant association for severe asthma exacerbations on chromosome 2p21.…”

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confidence: 99%

Immunology and genetics of asthma, and probiotics in the treatment of atopic dermatitis

Eigenmann

2021

Pediatric Allergy Immunology

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Immunology and genetics of asthma, and probiotics in the treatment of atopic dermatitisThis past year has been disrupting, but also seen positive challenges in many aspects. And we would like to start this first issue of 2021 with a positive message. COVID-19 vaccines are coming, and hopefully, they will largely contribute to controlling the spread of the pandemic. Common vaccines trigger an immune response by an antigen-driven stimulus. However, the SARS-CoV-2-induced pandemic control is addressed not only by classic vaccine strategies but also by new, RNA-based strategies. The first review of this issue by Eberhardt and Siegrist assesses the various immunization strategies and their limitations to the pediatric population. 1 In addition, with the second wave (or third wave for some regions) pediatricians will be faced with more patients suffering from the multisystem inflammatory syndrome in children (MIS-C). The second review also addresses COVID-19 in pediatrics and discusses potential explanations for progression from "classic" COVID-19 to MIS-C. 2Asthma is a common disease in childhood, with still unmet needs regarding the understanding of immune mechanisms of progressions, as well as optimization of treatment by immunomodulators. 3,4 The first study I wish to comment on in this editorial is published by Beatriz Sastre and colleagues who investigated immune mechanisms underlying the development of recurrent wheezing after bronchiolitis in infancy. 5 Cells obtained from nasopharyngeal aspirates were sorted by flow cytometry to isolate type 2 innate lymphoid cells (ILC2). Cell mRNA expression was analyzed for a variety of inflammatory factors, and a large panel of pro-inflammatory and immunomodulatory factors, as well as lipid mediators and nitrites, was evaluated by ELISA and Luminex. They observed a higher expression of the ST2 + IL-33 receptor in the ILC2 population from the bronchiolitis group. This expression receptor could be increased by the presence of IL-1β, IL-2, or lipid mediators such as cysteinyl leukotrienes (LTC4 or LTE4) or prostaglandin D2. They conclude by mentioning that bronchiolitis patients had a higher percentage of ILC2 cells in the nasal aspirate and that this population of cells, by providing specific inflammatory signals, could play a significant role in the development of wheezing episodes later in life. Other studies and a review have recently addressed cell-related mechanisms of asthma and confirm the recent interest in innate-immunity-related mechanisms of asthma. [6][7][8]

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“…Care of asthma exacerbations is a major clinical challenge to the physician, and this condition has been largely studied and reported in PAI 13,14 . Here, the authors used a genetic approach to explain possible treatment failures, as the prime role of genetics in asthma has been largely established earlier 15–17 …”

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confidence: 99%

Comments on vitamin D and sensitization, asthma treatment, and lung function development

Eigenmann

2021

Pediatric Allergy Immunology

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Comments on vitamin D and sensitization, asthma treatment, and lung function developmentAsthma is the common denominator for the first two reviews featured in this issue. Rossi et al. 1 comment and analyze the complex interactions between the respiratory syncytial virus (RSV) and the airway microbiota, highlighting the fact that viruses such as the RSV might increase the virulence of bacterial pathogens in the airways, but that also a disbalance in the airway microbiota may promote more severe RSV infections.The second review by a group of South-East Asian colleagues focusing on their regional area analyzes how the environment can contribute to our understanding of the pathogenesis of asthma with an emphasis on prevention strategies. 2 The food-induced enterocolitis syndrome (FPIES) is well known to you, but probably less when similar symptoms are provoked by drugs (DIES). Francesca Mori et al. 3 describe new cases and analyze the current literature with a focus on similarities and differences between FPIES and DIES.In the first original study selected in this editorial, Raquel Segovia-Orti and colleagues looked at the association between vitamin D status and allergen sensitization in a population of children living in the Balearic Islands. 4Logistic regression on data from 749 subjects after age adjustment showed that vitamin D deficiency was associated with sensitization to D. pteronyssinus and dog dander, whereas insufficient vitamin D was associated with cat dander and D. pteronyssinus sensitization. They conclude by suggesting that trials are needed to test the effectiveness of vitamin D supplementation against sensitization to specific allergens, rather than clinical symptoms.The role of dietary factors in allergy has been reported in several recent publications in PAI 5-7 ; in addition, the reader will find in recent publications investigations on the effect of vitamin D on the immune system, as well as on allergic diseases. 8-10 Additionally, you may find some interest to look at sensitization patterns reported recently in Northern Europe, and how they may differ from the Spanish study. 11

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Genome‐wide association study reveals a novel locus for asthma with severe exacerbations in diverse populations

Cited by 19 publications

References 33 publications

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

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

Immunology and genetics of asthma, and probiotics in the treatment of atopic dermatitis

Comments on vitamin D and sensitization, asthma treatment, and lung function development

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