| Title: | A genome-wide association study of asthma hospitalizations in adults |
| Journal: | The Journal of Allergy and Clinical Immunology |
| Published: | 2 Sep 2020 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/32890573/ |
| DOI: | https://doi.org/10.1016/j.jaci.2020.08.020 |
| URL: | https://www.ncbi.nlm.nih.gov/pmc/articles/7921212 |
Publication 18682
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Abstract
BACKGROUND: Little is known about the genetic determinants of severe asthma exacerbations.</p>
OBJECTIVES: We aimed to identify genetic variants associated with asthma hospitalizations.</p>
METHODS: We conducted a genome-wide association study of asthma hospitalizations in 34,167 white British adults with asthma, 1,658 of whom had at least 1 asthma-related hospitalization. This analysis was conducted by using logistic regression under an additive genetic model with adjustment for age, sex, body mass index, smoking status, and the first 5 principal components derived from genotypic data. We then analyzed data from 2 cohorts of Latino children and adolescents for replication and conducted quantitative trait locus and functional annotation analyses.</p>
RESULTS: At the chromosome 6p21.3 locus, the single-nucleotide polymorphism (SNP) rs56151658 (8 kb from the promoter of HLA-DQB1) was most significantly associated with asthma hospitalizations (for test allele A, odds ratio = 1.36 [95% CI = 1.22-1.52]; P = 3.11 × 10-8); 21 additional SNPs in this locus were associated with asthma hospitalizations at a P value less than 1 × 10-6. In the replication cohorts, multiple SNPs in strong linkage disequilibrium with rs56151658 were associated with severe asthma exacerbations at a P value of .01 or less in the same direction of association as in the discovery cohort. Three HLA genes (HLA-DQA2, HLA-DRB6, and HLA-DOB) were also shown to mediate the estimated effects of the SNPs associated with asthma hospitalizations through effects on gene expression in lung tissue.</p>
CONCLUSIONS: We identified strong candidate genes for asthma hospitalizations in adults in the region for class II HLA genes through genomic, quantitative trait locus, and summary data-based mendelian randomization analyses.</p>
19 Keywords
- Adult
- Asthma
- Cohort Studies
- Female
- Gene Frequency
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Genotype
- HLA-D Antigens
- HLA-DQ Antigens
- HLA-DQ beta-Chains
- HLA-DR beta-Chains
- Hospitalization
- Humans
- Male
- Middle Aged
- Polymorphism, Single Nucleotide
- Promoter Regions, Genetic
- United Kingdom
16 Authors
- Qi Yan
- Erick Forno
- Esther Herrera-Luis
- Maria Pino-Yanes
- Ge Yang
- Sam Oh
- Edna Acosta-Pérez
- Donglei Hu
- Celeste Eng
- Scott Huntsman
- José R. Rodriguez-Santana
- Michelle M. Cloutier
- Glorisa Canino
- Esteban G. Burchard
- Wei Chen
- Juan C. Celedón
1 Application
| Application ID | Title |
|---|---|
| 43252 | The prediction of asthma status using clinical and genetic variables |
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