large-scale sequencing studies8,31: targets of FMRP32, constituents of the N-methyl-D-aspartate receptor (NMDAR74) and activity-regulated cytoskeleton-associated protein complexes (ARCs75,76), as well as CNS and behavioral gene sets from MGI database version 635.Genes identified by data-driven analysis. The final systems genomic analysis was designed as an ‘agnostic’ approach, with the aim of integrating a large number of gene sets from different public sources, not necessarily conceptually related to psychiatric disorders, as this has been successful elsewhere70,77. We conducted this analysis to test whether additional gene sets were associated in addition to those from the 134 CNS-related gene sets. For this, first we merged together the LoF-intolerant gene set and the 134 sets in the CNS-related collection. Second, we selected additional gene set sources to encompass a comprehensive collection of biochemical pathways and gene regulatory interaction networks: 2,693 gene sets with direct experimental evidence and a size of 10–200 genes70 were extracted from Gene Ontology (GO78) database release 01/02/2016; 1,787 gene sets were extracted from the fourth ontology level of MGI database version 635; 1,585 gene sets were extracted from REACTOME79 version 55; 290 gene sets were extracted from KEGG80 release 04/2015; and 187 gene sets were extracted from OMIM81 release 01/02/2016.
