Association study designs for complex diseases

Assessing the association between DNA variants and disease has been used wi dely to identify regions of the genome and candidate genes that contribute to disease. However, there are numerous examples of associations that canno t be replicated, which has led to scepticism about the utility of the appro ach for common conditions. With the discovery of massive numbers of genetic markers and the development of better tools for genotyping, association st udies will inevitably proliferate. Now is the time to consider critically t he design of such studies, to avoid the mistakes of the past and to maximiz e their potential to identify new components of disease.