Unraveling the complex genetic underpinnings of asthma and allergic disorders.
OBJECTIVE
Asthma and other allergic diseases are complex genetic disorders that result from interactions between multiple genes and environmental factors. In this review, we summarize findings from candidate gene analyses, discuss the recent success of genome-wide association (GWA) studies, and outline challenges facing the field.


RESULTS
In the past year, five GWA studies have been reported for asthma, one for atopic dermatitis, and four for intermediate phenotypes using quantitative trait loci. These results have in general been more robust to replication than prior candidate gene studies, and have allowed the identification of novel loci for both asthma (i.e. 1q31, 9q21.31) and atopic dermatitis (11q13).


CONCLUSIONS
The integration of results from recent GWA studies with careful analyses of candidate gene associations studies has confirmed the importance of immune detection and TH2-cell mediated immune responses in the pathogenesis of allergic disease, and has raised new interest in the role of epithelial barrier function and tissue-level responses. GWA studies appear to provide a robust way to identify novel gene loci contributing to disease susceptibility. Dissecting gene-gene and gene-environment interactions, and exploring the contribution of epigenetic phenomena to allergic disease susceptibility remain important challenges to understanding the complex nature of asthma and other allergic diseases.
Swarr
Daniel T
DT
Department of Pediatrics, Baylor College of Medicine & Texas Children's Hospital, Texas, USA.
Hakonarson
Hakon
H
D001249:Asthma / Q000235:genetics* / Q000276:immunology; D003876:Dermatitis, Atopic / Q000235:genetics* / Q000276:immunology; D004198:Disease Susceptibility; D004781:Environmental Exposure; D044127:Epigenesis, Genetic / Q000276:immunology; D004843:Epistasis, Genetic / Q000276:immunology; D053263:Gene Regulatory Networks / Q000276:immunology*; D055106:Genome-Wide Association Study; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics; D040641:Quantitative Trait Loci / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology