{"doi":"10.1111/pai.70165","title":"Genotypes in the 17q12‐q21 asthma risk locus and early‐life viral wheezing illnesses","abstract":"Infections with rhinovirus (RV) or respiratory syncytial virus (RSV) are the two most common triggers of wheezing illnesses in preschoolers. These illnesses are leading causes of hospitalization in the early years and also represent a significant risk factor for developing childhood asthma.1, 2 While lower respiratory illnesses caused by RSV are preventable, there are no vaccines or antivirals available for RVs. This therapeutic gap highlights the critical need to identify the pathogenic mechanisms behind virus-induced wheezing illnesses and to develop new strategies for treatment or prevention. Genetic, environmental, and personal factors contribute to the risk of preschool wheezing illnesses. These include genes that regulate immune responses and cell-surface receptors utilized by viruses. A genomic region on chromosome 17q12-q21, which encodes the genes ORMDL3 and GSDMB, significantly increases the risk for viral wheeze.3 Interestingly, this region is also the most significant and replicated locus for childhood-onset asthma,4, 5 especially in children with a history of wheeze6 and/or RV wheeze.3 In a combined analysis of two birth cohorts, it was unable to resolve whether relationships between 17q12-q21 genotype, viral wheezing illnesses, and childhood asthma depended on the virus causing the initial wheezing episodes.3 Another limitation of previous studies is that they were conducted in children with genetic ancestry most similar to European populations. We sought to address these limitations by investigating the relationships between genetic variation at the 17q12-q21 locus and early-life viral wheezing illness in children from four birth cohorts participating in the Children's Respiratory and Environment Workgroup (CREW),7 a consortium funded by the NIH's Environmental Influences on Child Health Outcomes (ECHO) program.8 These children are diverse with respect to ancestry, geography, and socio-demographic factors associated with asthma. We tested for associations between single nucleotide polymorphisms (SNPs) across the extended 17q12-q21 region and time to RV- and RSV-specific wheezing illness and analyzed the role of parent-reported race. The study population consisted of 1475 children enrolled in four birth cohorts: the Tucson Children's Respiratory Study (TCRS), the Childhood Origins of Asthma study (COAST), the Urban Environment and Childhood Asthma (URECA) study, and the Infant Susceptibility to Pulmonary Infections and Asthma Following RSV Exposure (INSPIRE) study (Table 1). This work was approved by the institutional review boards at the participating institutions. SNPs were genotyped using a TaqMan assay as previously reported.9 Because of the strong LD among SNPs within each of the three regions,9 we selected one SNP from each region as a surrogate for other variants in those regions. To this end, we selected rs2941504 in the proximal region because it showed the least LD with the core region SNPs in CREW children who identified as White or Black9 and was an eQTL for PGAP3.10 We selected rs7216386 in the core region because it was previously associated with RV wheezing illness and is an eQTL for GSDMB and ORMDL3.3 In the distal region, we selected rs3859192 because it had the least LD with the core region SNPs9, 11 and was an eQTL for GSDMA.12 A parent or guardian provided written informed consent for their child. Parent-identified Black children comprised 32.1% of the subjects. RV wheezing illnesses occurred in 19.2% of children identified as White and 42.8% identified as Black. RSV wheezing illnesses occurred in 21.4% and 16.7% of children identified as White and Black, respectively. To investigate genotype effects on time to first viral wheezing illness in early life, we performed time-to-event analyses separately for RV and RSV wheezing illnesses during the first 3 years of life. We stratified this analysis by race due to differences in genetic architecture in this region. European ancestry is associated w","journal":"Pediatric Allergy and Immunology","year":2025,"id":553744,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9646,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":275876,"name":"Tebeb Gebretsadik","orcid":"0000-0003-4548-3010","position":1,"is_corresponding":false},{"id":1376361,"name":"Sweta Singh","orcid":null,"position":2,"is_corresponding":false},{"id":309405,"name":"Lisa Gress","orcid":null,"position":3,"is_corresponding":false},{"id":111245,"name":"Eneida A. Mendonca","orcid":"0000-0003-4297-9221","position":4,"is_corresponding":false},{"id":275868,"name":"Brittney M. Snyder","orcid":"0000-0001-8356-3965","position":5,"is_corresponding":false},{"id":519084,"name":"Amy Eapen","orcid":"0000-0003-1629-1511","position":6,"is_corresponding":false},{"id":326246,"name":"Petra LeBeau","orcid":"0000-0002-0883-9922","position":7,"is_corresponding":false},{"id":283093,"name":"Ronald E. Gangnon","orcid":"0000-0003-2587-6714","position":8,"is_corresponding":false},{"id":295465,"name":"Christine M. Seroogy","orcid":"0000-0002-0532-3701","position":9,"is_corresponding":false},{"id":110400,"name":"Leonard B. Bacharier","orcid":"0000-0003-0432-2704","position":10,"is_corresponding":false},{"id":256805,"name":"Robert F. Lemanske","orcid":null,"position":11,"is_corresponding":false},{"id":233436,"name":"Susan V. Lynch","orcid":"0000-0001-5695-7336","position":12,"is_corresponding":false},{"id":71916,"name":"Diane R. Gold","orcid":"0000-0001-8789-418X","position":13,"is_corresponding":false},{"id":275584,"name":"Rachel L. Miller","orcid":"0000-0002-4214-3347","position":14,"is_corresponding":false},{"id":110398,"name":"Daniel J. Jackson","orcid":"0000-0001-6938-2690","position":15,"is_corresponding":false},{"id":306761,"name":"Gurjit K. Khurana Hershey","orcid":"0000-0001-6663-977X","position":16,"is_corresponding":false},{"id":306763,"name":"Christine Cole Johnson","orcid":"0000-0002-6864-6604","position":17,"is_corresponding":false},{"id":306766,"name":"Fernando D. Martínez","orcid":"0000-0001-6094-2727","position":18,"is_corresponding":false},{"id":110407,"name":"Carole Ober","orcid":"0000-0003-4626-9809","position":19,"is_corresponding":false},{"id":275878,"name":"Tina V. Hartert","orcid":"0000-0001-7470-1166","position":20,"is_corresponding":false},{"id":110411,"name":"James E. Gern","orcid":"0000-0002-6667-4708","position":21,"is_corresponding":false},{"id":1451110,"name":"the ECHO Children's Respiratory and Environmental Workgroup","orcid":null,"position":22,"is_corresponding":false},{"id":572763,"name":"Nathan Schoettler","orcid":"0000-0001-9851-6352","position":0,"is_corresponding":true}],"reference_count":16,"raw_metadata":null,"created_at":"2026-07-19T02:54:45.872391Z","pmid":"40755347","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}