Genome‐wide association study of inhaled corticosteroid response in admixed children with asthma

Hernandez‐Pacheco, Natalia; Farzan, Niloufar; Francis, Ben; Karimi, Leila; Repnik, Katja; Vijverberg, Susanne J. H.; Soares, Patrícia; Schieck, Maximilian; Gorenjak, Mario; Forno, Erick; Eng, Celeste; Oh, Sam S.; Pérez‐Méndez, Lina; Berce, Vojko; Tavendale, Roger; Samedy‐Bates, Lesly‐Anne; Hunstman, Scott; Hu, Donglei; Meade, KKelley; Farber, Harold J.; Avila, Pedro C.; Serebrisky, Denise; Thyne, Shannon; Brigino-Buenaventura, Emerita; Rodríguez-Cintrón, William; Sen, Sunak; Kumar, Rajesh; LeNoir, Michael A.; Rodríguez‐Santana, José; Celedón, Juan C.; Mukhopadhyay, Somnath; Potočnik, Uroš; Pirmohamed, Munir; Verhamme, Katia; Kabesch, Michael; Palmer, Colin N.A.; Hawcutt, Daniel B; Flores, Carlos; Zee, Anke‐Hilse Maitland‐van der; Burchard, Esteban G.; Pino-Yanes, María

doi:10.1111/cea.13354

Cited by 53 publications

(73 citation statements)

References 49 publications

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“…Hernandez-Pacheco et al 44 conducted a meta-analysis of asthma exacerbations using 1347 admixed children with asthma treated with inhaled corticosteroids. No genome-wide significant loci were identified, but a locus near APOBEC3B and APO-BEC3C on chromosome 22q13.1 was suggestively significant and replicated in a meta-analysis of studies conducted on Europeans.…”

Section: Gwass Of Asthma Drug Responsementioning

confidence: 99%

“…No genome-wide significant loci were identified, but a locus near APOBEC3B and APO-BEC3C on chromosome 22q13.1 was suggestively significant and replicated in a meta-analysis of studies conducted on Europeans. 44 In the second study, Levin et al 45 assessed corticosteroid responsiveness in 244 African American subjects 12 years of age and older who were monitored while receiving inhaled corticosteroid therapy. Two variants surpassed the genome-wide significant threshold.…”

Section: Gwass Of Asthma Drug Responsementioning

confidence: 99%

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Advances in asthma and allergic disease genetics: Is bigger always better?

Schoettler

Rodríguez

Weidinger

et al. 2019

Journal of Allergy and Clinical Immunology

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This review focuses on genome-wide association studies (GWASs) of asthma and allergic diseases published between January 1, 2018, and June 30, 2019. During this time period, there were 38 GWASs reported in 19 articles, including the largest performed to date for many of these conditions. Overall, we learned that childhood-onset asthma is associated with the most independent loci compared with other defined groups of asthma and allergic disease cases; adult-onset asthma and moderate-to-severe asthma are associated with fewer genes, which are largely a subset of those associated with childhoodonset asthma. There is significant genetic overlap between asthma and allergic diseases, particularly with respect to childhood-onset asthma, which involves genes that reflect the importance of barrier function biology, and to HLA region genes, which are the most frequently associated genes overall in both groups of diseases. Although the largest GWASs in African American and Latino/Hispanic populations were reported during this period, they are still significantly underpowered compared with studies reported in populations of European ancestry, highlighting the need for larger studies, particularly in patients with childhood-onset asthma and allergic diseases, in these important populations that carry the greatest burden of disease.

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Section: Gwass Of Asthma Drug Responsementioning

confidence: 99%

Section: Gwass Of Asthma Drug Responsementioning

confidence: 99%

Advances in asthma and allergic disease genetics: Is bigger always better?

Schoettler

Rodríguez

Weidinger

et al. 2019

Journal of Allergy and Clinical Immunology

View full text Add to dashboard Cite

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“…Hernandez-Pacheco et al did not find any consistent association of 22 SNPs associated with treatment response by previous GWAS. 73 Similarly, Spear et al and Mak et al failed to replicate the association of SNPs associated with BDR by previous candidate-gene association studies or GWAS. 32,36 Differences in the statistical power of candidate-gene studies and GWAS and the analysis of different racial/ethnic groups could explain the inconsistent results among studies.…”

Section: Discussionmentioning

confidence: 99%

“…Altogether, eleven candidate-gene studies, [24][25][26][27][28][55][56][57][58][59] a meta-analysis of a candidate gene, 60 and six pharmacogenomic studies (one of them in adults but including replication in children) have been performed. 32,36,40,73,74,79 During this period, candidate-gene studies reported the association of genes previously described in pharmacogenetic studies of pediatric asthma with treatment response (ADRB2, GSDMB, FCER2, and VEGFA). 13,[16][17][18] Additionally, other candidate genes have been related for the first time to this phenotype in children (SPATS2L, ASB3, IL1RL1, MMP9, and COL2A1).…”

Section: Discussionmentioning

confidence: 99%

“…In 2019, two GWAS have assessed ICS response in pediatric asthma (Table 2). 73,74 Hernandez-Pacheco et al 73 presence of asthma exacerbations during the last 12 months, considering as exacerbations ER visits, hospitalizations, or the administration of OCS because of asthma. Fifteen independent SNPs were suggestively associated with ICS response (p-value≤5 × 10 −6 ) and one of them replicated in Europeans (n=1,697) at a nominal significance level (rs5995653, p-value=0.008).…”

Section: Pharmacogenomic Studies Of Ics Responsementioning

confidence: 99%

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<p>Pharmacogenetics of Pediatric Asthma: Current Perspectives</p>

Pérez-García¹,

Espuela‐Ortiz²,

Lorenzo-Díaz³

et al. 2020

PGPM

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Asthma is a chronic respiratory disease that affects 339 million people worldwide and has a considerable impact on the pediatric population. Asthma symptoms can be controlled by pharmacological treatment. However, some patients do not respond to therapy and continue suffering from symptoms, which impair the quality of life of patients and limit their daily activity. Genetic variation has been shown to have a role in treatment response. The aim of this review is to update the main findings described in pharmacogenetic studies of pediatric asthma published from

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Class II Human Leukocyte Antigen Variants Associate With Risk of Pegaspargase Hypersensitivity

Liu

Yang

Smith

et al. 2021

Clin Pharma and Therapeutics

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We conducted the first human leukocyte antigen (HLA) allele and genome‐wide association study to identify loci associated with hypersensitivity reactions exclusively to the PEGylated preparation of asparaginase (pegaspargase) in racially diverse cohorts of pediatric leukemia patients: St Jude Children’s Research Hospital’s Total XVI (TXVI, n = 598) and Children’s Oncology Group AALL0232 (n = 2,472) and AALL0434 (n = 1,189). Germline DNA was genotyped using arrays. Genetic variants not genotyped directly were imputed. HLA alleles were imputed using SNP2HLA or inferred using BWAkit. Analyses between genetic variants and hypersensitivity were performed in each cohort first using cohort‐specific covariates and then combined using meta‐analyses. Nongenetic risk factors included fewer intrathecal injections (P = 2.7 × 10−5 in TXVI) and male sex (P = 0.025 in AALL0232). HLA alleles DQB1*02:02, DRB1*07:01, and DQA1*02:01 had the strongest associations with pegaspargase hypersensitivity (P < 5.0 × 10−5) in patients with primarily European ancestry (EA), with the three alleles associating in a single haplotype. The top allele HLA‐DQB1*02:02 was tagged by HLA‐DQB1 rs1694129 in EAs (r2 = 0.96) and less so in non‐EAs. All single nucleotide polymorphisms associated with pegaspargase hypersensitivity reaching genome‐wide significance in EAs were in class II HLA loci, and were partially replicated in non‐EAs, as is true for other HLA associations. The rs9958628 variant, in ARHGAP28 (previously linked to immune response in children) had the strongest genetic association (P = 8.9 × 10−9) in non‐EAs. The HLA‐DQB1*02:02‐DRB1*07:01‐DQA1*02:01 associated with hypersensitivity reactions to pegaspargase is the same haplotype associated with reactions to non‐PEGylated asparaginase, even though the antigens differ between the two preparations.

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Genome‐wide association study of inhaled corticosteroid response in admixed children with asthma

Abstract: Background:Inhaled corticosteroids (ICS) are the most widely prescribed and effec-

Cited by 53 publications

References 49 publications

Advances in asthma and allergic disease genetics: Is bigger always better?

Advances in asthma and allergic disease genetics: Is bigger always better?

<p>Pharmacogenetics of Pediatric Asthma: Current Perspectives</p>

Class II Human Leukocyte Antigen Variants Associate With Risk of Pegaspargase Hypersensitivity

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