For disorders with sufficient data (AD, BIP, and SCZ), the results are consistent with an allelic spectrum and an etiological role for both rare and common variation. As an example, Figure 1b synthesizes current knowledge of SCZ as an empirical allelic spectrum map compared to a conceptual schematic from a 2008 review in this journal. 10 There are no known Mendelian variants, and power analyses can exclude common variants of modest effect (genotypic relative risk > 1.5 for allele frequencies > 0.1). There are multiple SVs that are rare, strong, but non-specific risk factors (Table 2), and 17 common variant associations of subtle effects (Table 3). There is an important component arising from common variation in hundreds of different loci (Box 3), and larger sample sizes are likely to convert many of these to genome-wide significance. The frequency region between 0.001–0.05 is under investigation by studies evaluating exon variation, and more should be known in 2012–2013. This allelic spectrum map might well be replicated for other psychiatric disorders should larger studies of both rare, uncommon, and common variation be achieved.
