Genetic heterogeneity of asthma phenotypes identified by a clustering approach

Valérie Siroux, Juan R. González, Emmanuelle Bouzigon, Ivan Curjuric, Anne Boudier, Medea Imboden, Josep Maria Anto, Ivo Gut, Deborah Jarvis, Mark Lathrop, Ernst Reidar Omenaas, Isabelle Pin, Mathias Wjst, Florence Demenais, Nicole Probst-Hensch, Manolis Kogevinas, Francine Kauffmann

    Research output: Contribution to journalArticleResearchpeer-review

    44 Citations (Scopus)


    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. Copyright © ERS 2014.
    Original languageEnglish
    Pages (from-to)439-452
    JournalEuropean Respiratory Journal
    Issue number2
    Publication statusPublished - 1 Feb 2014


    Dive into the research topics of 'Genetic heterogeneity of asthma phenotypes identified by a clustering approach'. Together they form a unique fingerprint.

    Cite this