Once investigators have chosen a candidate gene and suitable polymorphism, they commonly test the role of this gene in a sample of randomly chosen subjects with the disease (i.e., cases) and without the disease (i.e., controls). Such subject groups are relatively easy to obtain, giving the candidate gene approach an important advantage over the linkage mapping approach, which requires the analysis of families with multiple affected members. Additional advantages of the case-control study design over linkage-based methods include the following (Malhotra and Goldman 1999):