Candidate gene case-control studies

Two main approaches to the identification of genes are involved in polygenic diseases. Use of family studies has generally been the preferred approach up until recently, but this is only feasible if the genetic component of the disease is relatively strong and DNA samples are available from other family members. Population case-control studies are useful both as an alternative and an adjunct to family studies. These can involve either whole genome scanning or candidate gene approaches. While whole genome scanning is likely to be widely used in the future once more information on genome-wide single nucleotide polymorphism distributions is available, at present, candidate gene studies are more feasible. When performing candidate gene case-control studies factors such as study design, methods for recruitment of case and controls, selection of candidate genes, functional significance of polymorphisms chosen for study and statistical analysis require close attention to ensure that only genuine associations are detected. Some examples of the successful use of candidate gene case-control studies are discussed and, to illustrate some potential problems in the design and interpretation of association studies, some specific examples of association studies on cancer are considered.