In order to perform burden analyses, we compiled a series of lists:(1) Genes and loci implicated causally in ASD (updated from Betancur),18 all of which have also been implicated in ID, as well as genes and loci implicated in ID, but not yet in ASD (Tables S6A–S6D). Note that the list of genes and loci involved in ASD was updated independently of the data from AGP stage 1;6 thus, genes and loci were included only if there was independent evidence from other studies.
(2) Highly-brain-expressed genes defined by a log(RPKM [reads per kb per million reads]) > 4.5 by the BrainSpan resource (n = 5,610 genes).
(3) Functionally characterized control genes not expressed in the brain (log(RPKM) < 1; n = 5,410 genes).
(4) Postsynaptic density (PSD) genes.33
(5) Genes found to interact with fragile X mental retardation protein (FMRP).34
(6) Genes associated with neurological phenotypes compiled from the Human Phenotype Ontology (HPO) and Mammalian Phenotype Ontology (MPO).
(7) Genes grouped by their probability of haploinsufficiency (pHI)35 into three subgroups: pHI > 0.15 (n = 8,862 genes), pHI > 0.35 (n = 4,136 genes), and pHI > 0.55 (n = 2,214 genes).