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Article Dans Une Revue European Respiratory Journal Année : 2013

Genetic heterogeneity of asthma phenotypes identified by a clustering approach

1 Inserm, U823, Institut Albert Bonniot, Team of Environmental Epidemiology Applied to Reproduction and Respiratory Health, Grenoble
2 IGA, Université Joseph Fourier, Grenoble
3 ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Dr. Aiguader, 88, Barcelona
4 Dept of Mathematics, Autonomous University of Barcelona, Barcelona
5 CIBER Epidemiologia y Salud Pública (CIBERESP), Barcelona
6 INSERM, UMRS-946, Genetic Variation of Human Diseases Unit, Paris
7 U946 - Variabilité Génétique et Maladies Humaines
8 Unibas - Université de Bâle = University of Basel = Basel Universität
9 CREAL - Centre for Research in Environmental Epidemiology [Barcelona, Spain]
10 Universitat Pompeu Fabra, Dept de Cie`ncies Experimentals i de la Salut, Barcelona
11 IMIM - Hospital del Mar Medical Research Institute [Barcelona, Spain]
12 CNG - Centre National de Génotypage
13 CNAG - Centro Nacional de Analisis Genomico
14 Respiratory Epidemiology and Public Health, Imperial College, London, and MRC-HPA Centre for Environment and Health, London, UK
15 UiB - University of Bergen
16 Center for Clinical Research, Haukeland University Hospital, Bergen, Norway
17 IGA, Université Joseph Fourier, Grenoble
18 Dept of Pediatrics, CHU Grenoble, Grenoble
19 Comprehensive Pneumology Center (CPC), Helmholtz Zentrum Muenchen, German Research Center for Environmental Health (GmbH), Neuherberg
20 Department of Psychosomatic Medicine and Psychotherapy, Klinikum rechts d. Isar, Techn. Universitaet
21 IUH - Institut Universitaire d'Hématologie
22 Municipal Institute of Medical Research - IMIM [Barcelona, Spain]
23 Centre for Research in Environmental Epidemiology (CREAL), Municipal Institute of Medical Research (IMIM-Hospital del Mar), and CIBER Epidemiologia y Salud Pu ́ blica (CIBERESP), Barcelona, Spain, and National School of Public Health, Athens, Greece
24 CESP - Centre de recherche en épidémiologie et santé des populations

Résumé

The aim of the study was to identify genetic variants associated with refined asthma phenotypes enabling multiple features of the disease to be taken into account. Latent class analysis (LCA) was applied in 3001 adults ever having asthma recruited in the frame of three epidemiological surveys (the European Community Respiratory Health Survey (ECRHS), the Swiss Study on Air Pollution and Lung Disease in Adults (SAPALDIA) and the Epidemiological Study on the Genetics and Environment of Asthma (EGEA)). 14 personal and phenotypic characteristics, gathered from questionnaires and clinical examination, were used. A genome-wide association study was conducted for each LCA-derived asthma phenotype, compared to subjects without asthma (n53474). The LCA identified four adult asthma phenotypes, mainly characterised by disease activity, age of asthma onset and atopic status. Associations of genome-wide significance (p,1.25610-7) were observed between ‘‘active adult-onset nonallergic asthma’’ and rs9851461 flanking CD200 (3q13.2) and between ‘‘inactive/ mild nonallergic asthma’’ and rs2579931 flanking GRIK2 (6q16.3). Borderline significant results (2.5610-7,p,8.2610-7) were observed between three single nucleotide polymorphisms (SNPs) in the ALCAM region (3q13.11) and ‘‘active adult-onset nonallergic asthma’’. These results were consistent across studies. 15 SNPs identified in previous genome-wide association studies of asthma have been replicated with at least one asthma phenotype, most of them with the ‘‘active allergic asthma’’ phenotype. Our results provide evidence that a better understanding of asthma phenotypic heterogeneity helps to disentangle the genetic heterogeneity of asthma.
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Dates et versions

hal-04315201 , version 1 (30-11-2023)

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V. Siroux, J R Gonzalez, Emmanuelle Bouzigon, Ivan Curjuric, Anne Boudier, et al.. Genetic heterogeneity of asthma phenotypes identified by a clustering approach. European Respiratory Journal, 2013, 43 (2), pp.439 - 452. ⟨10.1183/09031936.00032713⟩. ⟨hal-04315201⟩
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