Risk variants for neurodevelopmental disorders such as schizophrenia (SZ) include both common single-nucleotide variants (SNVs) with small effects sizes (Schizophrenia Working Group of the Psychiatric Genomics Consortium, 2014) and copy-number variations (CNVs) with greater penetrance (CNV and Schizophrenia Working Groups of the Psychiatric Genomics Consortium; Psychosis Endophenotypes International Consortium, 2017). The majority of SZ-associated SNVs reside in genomic loci outside of coding regions (Schizophrenia Working Group of the Psychiatric Genomics Consortium, 2014), and may function as cis-acting expression quantitative trait loci (cis-eQTLs) (Fromer et al., 2016); however, they are frequently associated with genes that have limited functional annotation, making the connection between gene function and disease risk difficult to untangle. Moreover, because SZ-associated CNVs are large structural deletions or duplications of genomic sequence that generally encompass multiple genes (CNV and Schizophrenia Working Groups of the Psychiatric Genomics Consortium; Psychosis Endophenotypes International Consortium, 2017), defining the gene(s) responsible for disease risk can be difficult to resolve.
