Genome-wide association studies in the genetics of asthma.
The field of asthma genetics has progressed rapidly over the past decade, implicating many genes and variants in the etiology of this complex disease. However, many of these factors have failed to replicate consistently, indicating a high false-positive rate and/or insufficient power for the detection of small effects. Technological limitations also have restricted the potential to detect novel mechanisms, fostering a dependence on existing knowledge. Since its inception almost 4 years ago, genome-wide association (GWA) has transformed genetic studies of multifactorial traits and yielded unprecedented insights into mechanisms of causation. Asthma is at the forefront of this revolution, as it uses GWA to map not only genetic determinants of clinical status but also transcript and protein abundance and structural (copy number) variants that may underlie disease susceptibility. In this review, we consider the applications of GWA data to asthma and describe the factors likely to influence the procedure's success.
Willis-Owen
Saffron A G
SA
Molecular Genetics, National Heart and Lung Institute, London, United Kingdom. s.willis-owen@imperial.ac.uk
Cookson
William O
WO
Moffatt
Miriam F
MF
D001249:Asthma / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D000094524:Gasdermins
D008565:Membrane Proteins; D009363:Neoplasm Proteins; C527978:GSDMB protein, human; D000094524:Gasdermins; C464399:ORMDL3 protein, human