Before we had the tools to systematically interrogate variation throughout the human genome, there were two schools of thought in sometimes mortal combat. As Robert Shields reminds us in his editorial, some argued for the common-disease common-variant model (CD-CV), postulating an important role for common variants in common disease, while others argued that a great diversity of different rare variants were most likely the primary drivers of common diseases. The International HapMap Project, and the genomewide association studies (GWAS) it enabled, were motivated in part by the CDCV model.

Before GWAS, strong theoretical arguments were marshaled in support of either rare variants [1] or common variants [2], but few data were available to resolve the dispute. GWAS changed that by allowing us a (nearly) comprehensive evaluation of the role of common variation in human disease.