Figure 3b encapsulates experience with sample size and numbers of significant associations. Some disorders have a fortuitous architecture; e.g., inflammatory bowel disease obtained a considerable number of findings with relatively small samples. For most other complex traits, the path is slower but, with sufficient samples, discovery becomes linear. Figure 3c shows an idealized cartoon of the sigmoid-like discovery process from “dead zone” to asymptote. We suggest that the goal is to get to a “good enough” point where most genes are identified at least once and the majority of genes in salient biological processes are highlighted. This can provide an etiologic scaffold for studies that use other methods to identify interacting partners in gene networks and pathways that underlie pathogenesis. There may be on the order of 1,000 genes involved in schizophrenia (43) (for comparison, ~13,000 genes are expressed in brain and ~2,000 at the synapse). Most of the nine PGC disorder working groups have identified at least one genome-wide significant association, several are accumulating moderate numbers of loci, and schizophrenia and MDD appear to be in the linear phase (Table 1b).
