Genetic and genomic approaches to asthma: new insights for the origins

被引:75
|
作者
Zhang, Youming [1 ]
Moffatt, Miriam F. [1 ]
Cookson, William O. C. [1 ]
机构
[1] Univ London Imperial Coll Sci Technol & Med, Div Resp Sci, Mol Genet Grp, London, England
基金
英国惠康基金;
关键词
asthma; IgE; genetics; genome-wide association studies; genomics; WIDE ASSOCIATION; GENOMEWIDE ASSOCIATION; IN-VIVO; GASTROINTESTINAL-TRACT; INFLAMMATORY RESPONSE; SUSCEPTIBILITY LOCI; POSITIONAL CLONING; CHROMOSOME; 13Q14; DNA METHYLATION; T-CELLS;
D O I
10.1097/MCP.0b013e32834dc532
中图分类号
R56 [呼吸系及胸部疾病];
学科分类号
摘要
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.
引用
收藏
页码:6 / 13
页数:8
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