We then examined “co-morbid” groupings, for example, CNVs that are shared by two disorders such as ASD and ID, or CNVs found in 3 diagnostic groups (Table S4, available online). CNVs that only overlapped among ID-ASD CNVs were enriched for cell junction (p=.01), calcium-independent cell–cell adhesion (p=.03), and protein heterodimerization activity (p=.03). Significant CNVs that only overlapped with ID-schizophrenia identified endoplasmic reticulum membrane (p<.001) and glycerophospholipid biosynthetic process (p=.003). Significant results from “ID-ASD-schizophrenia” grouping included GABA receptor activity (p=.003), synaptic transmission (p=.006), and vesicle (p=.006). Interesting gene mechanisms emerged from the relatively “pure” groupings (Table S4, available online). For example, isolated ID processes included tumor necrosis factor binding (p<.001), positive regulation of apoptosis (p=.02), and actin cytoskeleton organization (p=.03). Channel regulator activity (p=.03) was the only significant process for isolated schizophrenia. Pathway analysis of gene groupings determined by broad criteria replicated many of the findings described above (Table S5, available online).
