Herrera-Luis, Esther and Ortega, Victor E. and Ampleford, Elizabeth J. and Sio, Yang Yie and Granell, Raquel and de Roos, Emmely and Terzikhan, Natalie and Vergara, Ernesto Elorduy and Hernandez-Pacheco, Natalia and Perez-Garcia, Javier and Martin-Gonzalez, Elena and Lorenzo-Diaz, Fabian and Hashimoto, Simone and Brinkman, Paul and Jorgensen, Andrea L. and Yan, Qi and Forno, Erick and Vijverberg, Susanne J. and Lethem, Ryan and Espuela-Ortiz, Antonio and Gorenjak, Mario and Eng, Celeste and Gonzalez-Perez, Ruperto and Hernandez-Perez, Jose M. and Poza-Guedes, Paloma and Sardon, Olaia and Corcuera, Paula and Hawkins, Greg A. and Marsico, Annalisa and Bahmer, Thomas and Rabe, Klaus F. and Hansen, Gesine and Kopp, Matthias Volkmar and Rios, Raimon and Cruz, Maria Jesus and Gonzalez-Barcala, Francisco-Javier and Maria Olaguibel, Jose and Plaza, Vicente and Quirce, Santiago and Canino, Glorisa and Cloutier, Michelle and Del Pozo, Victoria and Rodriguez-Santana, Jose R. and Korta-Murua, Javier and Villar, Jesus and Potocnik, Uros and Figueiredo, Camila and Kabesch, Michael and Mukhopadhyay, Somnath and Pirmohamed, Munir and Hawcutt, Daniel B. and Melen, Erik and Palmer, Colin N. and Turner, Steve and Maitland-van der Zee, Anke H. and von Mutius, Erika and Celedon, Juan C. and Brusselle, Guy and Chew, Fook Tim and Bleecker, Eugene and Meyers, Deborah and Burchard, Esteban G. and Pino-Yanes, Maria (2022) Multi-ancestry genome-wide association study of asthma exacerbations. PEDIATRIC ALLERGY AND IMMUNOLOGY, 33 (6): e13802. ISSN 0905-6157, 1399-3038
Full text not available from this repository. (Request a copy)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. 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 x 10(-5)) 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. 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 (ORT allele) = 0.82, p = 9.05 x 10(-6) and replication: ORT allele = 0.89, p = 5.35 x 10(-3)) and rs943126 from pantothenate kinase 1 (PANK1) (discovery: ORC allele = 0.85, p = 3.10 x 10(-5) and replication: ORC allele = 0.89, p = 1.30 x 10(-2)). Both variants regulate gene expression of genes where they locate and DNA methylation levels of nearby genes in whole blood. Conclusions: This multi-ancestry study revealed novel suggestive regulatory loci for asthma exacerbations located in genomic regions participating in inflammation and host defense.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | EFFICIENT; ADHESION; EXTL2; TOOL; asthma exacerbations; EXTL2; GWAS; PANK1; single-nucleotide polymorphism |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Kinder- und Jugendmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 19 Sep 2023 09:13 |
| Last Modified: | 19 Sep 2023 09:13 |
| URI: | https://pred.uni-regensburg.de/id/eprint/58845 |
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