Genetic and genomic approaches to asthma: new insights for... : Current Opinion in Pulmonary Medicine (original) (raw)

ASTHMA: Edited by Nicola A. Hanania

new insights for the origins

Molecular Genetics Group, Division of Respiratory Sciences, Imperial College London, London, UK

Correspondence to Dr Youming Zhang, Molecular Genetics Group, National Heart and Lung Institute, Dovehouse Street, London, SW3 6LY, UK. E-mail: [email protected]

Abstract

Purpose of review

The aim is to update current understanding of the genes identified by the recent genome-wide association studies (GWASs) of asthma and its associated traits. The review also discusses how to dissect the functional roles of novel genes in future research.

Recent findings

More than 10 GWAS aimed at identifying the genes underlying asthma and relevant traits have been published in the past 3 years. The largest of these was from the GABRIEL consortium, which discovered that the IL18R1, IL33, SMAD3, ORMDL3, HLA-DQ and IL2RB loci were all significantly associated with asthma. Many novel asthma genes, including those previously identified by positional cloning, are expressed within the respiratory epithelium, emphasizing the importance of epithelial barriers in causing asthma . The genes controlling IgE levels have surprisingly little overlap with the genes mediating asthma susceptibility, suggesting that atopy is secondary to asthma rather than a primary driver of the disease. The next challenge will be the systematic analysis of the precise functions of these genes in the pathogenesis of asthma.

Summary

GWAS have uncovered many novel genes underlying asthma and detailed functional dissection of their roles in asthma will point the way to new therapies for the disease.