1. Genetic heterogeneity of asthma phenotypes identified by a clustering approach
- Author
-
Valérie Siroux, Nicole Probst-Hensch, M Lathrop, Florence Demenais, Ivo Gut, Juan R. González, Emmanuelle Bouzigon, Deborah Jarvis, M. Wjst, Manolis Kogevinas, Ivan Curjuric, Anne Boudier, Francine Kauffmann, Medea Imboden, Isabelle Pin, Ernst Omenaas, and Josep M. Antó
- Subjects
Pulmonary and Respiratory Medicine ,Adult ,Male ,medicine.medical_specialty ,Genotype ,Single-nucleotide polymorphism ,Disease ,Polymorphism, Single Nucleotide ,Cohort Studies ,Genetic Heterogeneity ,immune system diseases ,Epidemiology ,medicine ,Cluster Analysis ,Humans ,Genetic association ,Asthma ,Genetic heterogeneity ,business.industry ,Genetic Variation ,Reproducibility of Results ,Middle Aged ,medicine.disease ,Phenotype ,Latent class model ,3. Good health ,respiratory tract diseases ,Immunology ,Female ,France ,business ,Switzerland ,Follow-Up Studies ,Genome-Wide Association Study - Abstract
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 (n=3474). The LCA identified four adult asthma phenotypes, mainly characterised by disease activity, age of asthma onset and atopic status. Associations of genome-wide significance (p1.25 × 10(-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 (2.5 × 10(-7)p8.2 × 10(-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.
- Published
- 2014