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Multi-ancestry genome-wide association study of asthma exacerbations.
- Source :
-
Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology [Pediatr Allergy Immunol] 2022 Jun; Vol. 33 (6), pp. e13802. - Publication Year :
- 2022
-
Abstract
- Background: Asthma exacerbations are a serious public health concern due to high healthcare resource utilization, work/school productivity loss, impact on quality of life, and risk of mortality. The genetic basis of asthma exacerbations has been studied in several populations, but no prior study has performed a multi-ancestry meta-analysis of genome-wide association studies (meta-GWAS) for this trait. We aimed to identify common genetic loci associated with asthma exacerbations across diverse populations and to assess their functional role in regulating DNA methylation and gene expression.<br />Methods: A meta-GWAS of asthma exacerbations in 4989 Europeans, 2181 Hispanics/Latinos, 1250 Singaporean Chinese, and 972 African Americans analyzed 9.6 million genetic variants. Suggestively associated variants (p ≤ 5 × 10 <superscript>-5</superscript> ) were assessed for replication in 36,477 European and 1078 non-European asthma patients. Functional effects on DNA methylation were assessed in 595 Hispanic/Latino and African American asthma patients and in publicly available databases. The effect on gene expression was evaluated in silico.<br />Results: One hundred and twenty-six independent variants were suggestively associated with asthma exacerbations in the discovery phase. Two variants independently replicated: rs12091010 located at vascular cell adhesion molecule-1/exostosin like glycosyltransferase-2 (VCAM1/EXTL2) (discovery: odds ratio (OR <subscript>T allele</subscript> ) = 0.82, p = 9.05 × 10 <superscript>-6</superscript> and replication: OR <subscript>T allele</subscript>  = 0.89, p = 5.35 × 10 <superscript>-3</superscript> ) and rs943126 from pantothenate kinase 1 (PANK1) (discovery: OR <subscript>C allele</subscript>  = 0.85, p = 3.10 × 10 <superscript>-5</superscript> and replication: OR <subscript>C allele</subscript>  = 0.89, p = 1.30 × 10 <superscript>-2</superscript> ). Both variants regulate gene expression of genes where they locate and DNA methylation levels of nearby genes in whole blood.<br />Conclusions: This multi-ancestry study revealed novel suggestive regulatory loci for asthma exacerbations located in genomic regions participating in inflammation and host defense.<br /> (© 2022 The Authors. Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)
Details
- Language :
- English
- ISSN :
- 1399-3038
- Volume :
- 33
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 35754128
- Full Text :
- https://doi.org/10.1111/pai.13802