ArticleGenome medicine2022
Fine-mapping studies distinguish genetic risks for childhood- and adult-onset asthma in the HLA region.
Article in Genome medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 15 citations in OpenAlex.
- Genetic research on childhood obesity and asthma: exploring genetic risk factors and biological mechanisms.Pediatric research · 2026Review
- Post-genome-wide association study variant-to-function challenges in asthma research.The Journal of allergy and clinical immunology · 2026Review
- Mechanisms and therapeutic strategies of asthma: from bench to bedside.Signal transduction and targeted therapy · 2026Review
- Sequencing and health data resource of children of African ancestry.Genetics in medicine : official journal of the American College of Medical Genetics · 2026Article
- Integrative multi-omics reveals that downregulation of HLA-DPA1/DPB1 drives macrophage immune-metabolic dysregulation in pediatric asthma.Frontiers in immunology · 2026Article
- Exploring the genetic architecture of multiple long-term conditions using a genome-wide association study in the UK Biobank population.Scientific reports · 2025Article
- BAYESIAN VARIABLE SELECTION IN A COX PROPORTIONAL HAZARDS MODEL WITH THE "SUM OF SINGLE EFFECTS" PRIOR.ArXiv · 2025Article
- Update on the genetics of allergic diseases.The Journal of allergy and clinical immunology · 2025Review
- Maternal asthma and newborn DNA methylation.Clinical epigenetics · 2025Article
- Genomic variants association with selective hypersensitivity reactions to amoxicillin and clavulanic acid.Allergy · 2025Article
- Copy Number Variation in Asthma: An Integrative Review.Clinical reviews in allergy & immunology · 2025Review
- Causal relationship between asthma and ankylosing spondylitis: A bidirectional two-sample univariable and multivariable Mendelian randomization study.Open medicine (Warsaw, Poland) · 2025Article
- Article
- Asthma-Genomic Advances Toward Risk Prediction.Clinics in chest medicine · 2024Review
- Race/ethnicity-stratified fine-mapping of the MHC locus reveals genetic variants associated with late-onset asthma.Frontiers in genetics · 2023Article
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Authors and funding
13 authors at 4 institutions in 1 country.
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Abstract
backgroundGenome-wide association studies of asthma have revealed robust associations with variation across the human leukocyte antigen (HLA) complex with independent associations in the HLA class I and class II regions for both childhood-onset asthma (COA) and adult-onset asthma (AOA). However, the specific variants and genes contributing to risk are unknown.
methodsWe used Bayesian approaches to perform genetic fine-mapping for COA and AOA (n=9432 and 21,556, respectively; n=318,167 shared controls) in White British individuals from the UK Biobank and to perform expression quantitative trait locus (eQTL) fine-mapping in immune (lymphoblastoid cell lines, n=398; peripheral blood mononuclear cells, n=132) and airway (nasal epithelial cells, n=188) cells from ethnically diverse individuals. We also examined putatively causal protein coding variation from protein crystal structures and conducted replication studies in independent multi-ethnic cohorts from the UK Biobank (COA n=1686; AOA n=3666; controls n=56,063).
resultsGenetic fine-mapping revealed both shared and distinct causal variation between COA and AOA in the class I region but only distinct causal variation in the class II region. Both gene expression levels and amino acid variation contributed to risk. Our results from eQTL fine-mapping and amino acid visualization suggested that the HLA-DQA1*03:01 allele and variation associated with expression of the nonclassical HLA-DQA2 and HLA-DQB2 genes accounted entirely for the most significant association with AOA in GWAS. Our studies also suggested a potentially prominent role for HLA-C protein coding variation in the class I region in COA. We replicated putatively causal variant associations in a multi-ethnic cohort.
conclusionsWe highlight roles for both gene expression and protein coding variation in asthma risk and identified putatively causal variation and genes in the HLA region. A convergence of genomic, transcriptional, and protein coding evidence implicates the HLA-DQA2 and HLA-DQB2 genes and HLA-DQA1*03:01 allele in AOA.
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