Unfortunately, unlike AD, no Mendelian forms of BIP and SCZ have been identified. 41 However, rare (frequency < 0.5%) but potent (genotypic relative risk, GRR, 5–20) SVs play a role in a small proportion of cases with SCZ (Table 2, Figure S1). None is fully penetrant, and nearly all appear to be non-specific as risk is often increased for SCZ, ASD, developmental delay, mental retardation, epilepsy, somatic dysmorphism, and extremes of body mass and head size. Most of these SV regions are fairly large (hundreds of kb to mb) and generally center on SV hotspots. 42 Two rare SVs affect single genes (NRXN1 and VIPR2) 43,44 offering opportunities for down-stream functional studies. Pathway analyses of genes intersected by rare SV suggest enrichment for neuronal processes of plausible etiological relevance (e.g., post-synaptic signaling). 45–47 The SV regions in Table 2 probably represent “low-hanging fruit” and more discoveries are likely with application of improved technologies for SV detection to larger samples. 15
