Models of complex genetic etiology. Risk variants are grouped according to their frequency in the population (x-axis) and their penetrance (y-axis). The penetrance of a disease-causing mutation is the proportion of individuals with the mutation who exhibit clinical symptoms. Zones A and B indicate risk variation assayed in genome-wide association studies (GWAS), and zone C indicates variants assayed by studies of copy number variation (CNV). Zone C also includes rare variants of intermediate penetrance that will be accessible to exomic and genomic sequencing (adapted from McCarthy et al. ).