Youming Zhang1, Miriam F Moffatt, William O C Cookson. 1. Molecular Genetics Group, Division of Respiratory Sciences, Imperial College London, Dovehouse Street, London, UK. y.zhang@imperial.ac.uk
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.
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.
Authors: Joanna Smolonska; Gerard H Koppelman; Cisca Wijmenga; Judith M Vonk; Pieter Zanen; Marcel Bruinenberg; Ivan Curjuric; Medea Imboden; Gian-Andri Thun; Lude Franke; Nicole M Probst-Hensch; Peter Nürnberg; Roland A Riemersma; Constant P van Schayck; Daan W Loth; Guy G Brusselle; Bruno H Stricker; Albert Hofman; André G Uitterlinden; Lies Lahousse; Stephanie J London; Laura R Loehr; Ani Manichaikul; R Graham Barr; Kathleen M Donohue; Stephen S Rich; Peter Pare; Yohan Bossé; Ke Hao; Maarten van den Berge; Harry J M Groen; Jan-Willem J Lammers; Willem Mali; H Marike Boezen; Dirkje S Postma Journal: Eur Respir J Date: 2014-07-03 Impact factor: 16.671