Candidate gene association studies and evidence for gene-by-gene interactions.

Candidate gene studies in asthma are a powerful and valuable tool in asthma genetics. Although the quality of small-scale, freely associating studies has been questionable, increasingly serious efforts are made to establish, replicate, and verify association results. Association studies may help us to better understand the mechanisms underlying asthma. They may create hypotheses and help to direct functional studies to targets that are likely to give valuable results. However, they should not be over-interpreted; only biologic proof can verify associations between genetic variations and a certain disease outcome. The insight that gene-by-gene and gene-by-environment interactions may be crucial for understanding and pinpoint the complex mechanisms of genetic regulation of multifactorial diseases has gained momentum in the last years when technical improvement allowed for the effective genotyping and analysis of great numbers of polymorphisms in large populations. It can be expected that from this area of research new and exciting results will follow soon.