The advantage of performing a study focused on one or few candidate genes or regions is cost efficiency. A relatively small number of markers will need to be genotyped to capture most of the common variation in the candidate region. However, de-novo candidate gene studies, in which candidates are selected entirely on the basis of their supposed biological significance, without any previous statistical evidence that the region they are located in is implicated, have had very low success rates even when well-designed 10. Candidate gene/region studies should therefore follow genomic linkage or association studies that have already implicated the region. Linkage studies are designed to indicate evidence of relatively rare variants with big effects, whereas association studies are powered to pick up common variants with modest effects. Following up linkage signals with population-based association study might not be the optimal strategy and this needs to be taken into account when selecting both the individuals and the markers to genotype in the follow up study. Alternatively, candidate genes can be selected from biological pathways which harbour other previously associated risk loci.
