Change in smoking status after low-dose spiral chest CT screening for lung cancer: opportunity for smoking intervention.

which needs further replication itself to increase the likelihood that the reported association is real. Nevertheless, these studies, as well as failures to replicate, should be published to evolve a full picture of a gene’s possible effects. Much can be learned from these findings and, in the end, they may be even more important for our understanding of genetics and disease mechanisms in complex diseases than straightforward replication. Blakey et al studied five positionally cloned genes, initially found in linkage and association studies in children. They now aimed to replicate associations with asthma, wheezing and IgE in their large British population sample. They found small but significant effects for polymorphisms in DPP10 and ADAM33 (and borderline for GPR154), with odds ratios of around 1.1 per allele. Is this the final verdict on the role of these genes in asthma? Rather not. Although this is a large and well phenotyped cross-sectional and probably unbiased population sample, it is a snapshot in time. The individuals studied were born in 1 week of 1958 in Britain. It may be assumed that environmental factors were very different at the time these individuals developed their asthma compared with children growing up nowadays. Looking back on the second half of the 20th century we have witnessed rising prevalence rates for asthma, and fundamental changes in lifestyle, diet, and personal and meta-environments. It could very well be that asthma of today’s children and youth is the result of mechanisms different from those relevant for asthma development 50 years ago. However, when associations are found consistently across time, this could point to very basic and timeless asthma mechanisms. This is nothing but a hypothesis—but one to consider when indulging in replication studies such as this that look simple at first glance but may hold more food for thought than expected.