Candidate-gene approaches for studying complex genetic traits: practical considerations

Association studies with candidate genes have been widely used for the study of complex diseases. However, this approach has been criticized because of nonreplication of results and limits on its ability to include all possible causative genes and polymorphisms. These challenges have led to pessimism about the candidate-gene approach and about the genetic analysis of complex diseases in general. We believe that these criticisms can be usefully countered with an appeal to the principles of epidemiological investigation.