2022 conference-abstract

Multi-ancestral meta-analysis yields novel genetic loci for asthma exacerbations

E. Herrera Luis, V E Ortega, E J Ampleford, Y Y Sio, R Granell, E De Roos, N Terzikhan, E Elorduy Vergara, N Hernandez-Pacheco, J Perez-Garcia, E Martin-Gonzalez, F Lorenzo-Diaz, S Hashimoto, P Brinkman, A L Jorgensen, Qunxiang Yan, E Forno, S J Vijverberg, R Lethem, A Espuela-Ortiz, M Gorenjak, C Eng, R González-Pérez, J M Hernández-Pérez, P Poza-Guedes, O Sardón, P Corcuera, G A Hawkins, A Marsico, T Bahmer, K F Rabe, G Hansen, M V Kopp, R Rios, M J Cruz, Francisco Jose González-Barcala, V Plaza, S Quirce, G Canino, M Cloutier, V Del Pozo, José Rodríguez‐Santana, J Korta-Murua, J Villar, U Potočnik, C Figueiredo, M Kabesch, S Mukhopadhyay, Munir Pirmohamed, D B Hawcutt, E Melén, C N Palmer, S Turner, Anke H. Maitland‐van der Zee, E Von Mutius, J. C. Celedón, G Brusselle, F T Chew, E Bleecker, D Meyers, E G Burchard, M Pino-Yanes

0Citations signalées, ce qui n’est pas une note de qualité

55Institutions déclarées

12Pays d’affiliation déclarés

Rattachement africain : es, us, sg, gb, be, nl, de, se, si, ch, br, pr. Niveau de preuve : code pays fourni par la source.

Le résumé fourni par la source

Background: Asthma exacerbations (AEs) impact quality of life, productivity, and healthcare costs, and can even be life-threatening. Therefore, identifying potential biomarkers to prevent AEs is a priority in asthma research. Aim: To identify susceptibility loci associated with AEs in individuals from multiple ancestral backgrounds. Methods: AEs were defined based on the presence of asthma-related hospitalizations, acute emergency care, school absences, or oral corticosteroids use in the last 6 to 24 months. A meta-analysis of genome-wide association studies (GWAS), analysing 9.6 million genetic variants, was conducted in 9,392 patients with asthma (4,989 of European-descent, 2,181 Hispanic/Latinos, 1,250 Singaporean Chinese, and 972 African Americans). A total of 36,477 European and 1,078 non-European subjects with asthma were included in the replication stage. Functional effects of genetic variation were investigated in silico and with DNA methylation data from 595 individuals. Results: From the 126 independent variants suggestively associated in the discovery phase (p≤5×10-5), two loci at the vascular cell adhesion molecule-1/exostosin like glycosyltransferase-2 region (VCAM1/EXTL2, rs12091010) and the pantothenate kinase 1 gene (PANK1, rs943126) were consistently replicated: p=5.35x10-3 and p=1.30x10-2, respectively. These were associated with DNA methylation levels and gene expression of nearby genes in whole blood. Conclusions: The largest multi-ancestry meta-analysis of GWAS of AEs identified two regulatory loci at genes involved in host defence and inflammation. Supported by MCIN/AEI/10.13039/501100011033 (SAF2017-83417R & PID2020-116274RB-I00) & fellowship PRE2018-083837 MINECO/AEI/FEDER, UE.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.

Le contrôle bibliographique ouvert

DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.

Titre Crossref: Multi-ancestral meta-analysis yields novel genetic loci for asthma exacerbations
Date Crossref: 04/09/2022
Éditeur: European Respiratory Society
Type: proceedings-article

Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.

Les institutions déclarées

Universidad de La Laguna Mayo Clinic in Arizona Wake Forest University National University of Singapore University of Bristol Ghent University Hospital Erasmus MC Helmholtz Munich Karolinska Institutet Stockholm South General Hospital Centro de Investigación Biomédica en Red de Enfermedades Respiratorias University of Amsterdam University of Liverpool Columbia University Irving Medical Center University of Pittsburgh Children's Hospital of Pittsburgh Utrecht University Amsterdam University Medical Centers University of Maribor University of California, San Francisco Hospital Universitario de Canarias Hospital Universitario Nuestra Señora de Candelaria University of the Basque Country Biogipuzkoa Health Research Institute LungenClinic Grosshansdorf Medizinische Hochschule Hannover University of Bern University Hospital of Bern University Hospital Schleswig-Holstein University Children’s Hospital Bern German Center for Lung Research University of Lübeck Universidade Federal da Bahia Centro de Investigación en Red en Enfermedades Cardiovasculares Vall d'Hebron Hospital Universitari Complejo Hospitalario Universitario de Santiago Complejo Hospitalario de Navarra Hospital de Sant Pau Hospital La Paz Institute for Health Research University of Puerto Rico System University of Connecticut Hospital Universitario Fundación Jiménez Díaz Centro de Neumologia Pediatrica Hospital Universitario de Gran Canaria Doctor Negrín University Hospital Regensburg Brighton and Sussex Medical School University of Dundee Ninewells Hospital Royal Alexandra Children's Hospital Alder Hey Children's Hospital Sachs' Children and Youth Hospital University of Aberdeen Ludwig-Maximilians-Universität München University of Arizona University of San Francisco

Une affiliation ne permet pas de déduire la nationalité d’un auteur.

Les sujets associés

Nutrition, Genetics, and DiseaseAsthma and respiratory diseases

Consulter la publication primaire Ouvrir le DOI