Psychiatric disorders affect more than 25% of the population in any given year and are a leading cause of worldwide disability (Global Burden of Disease Injury Incidence Prevalence Collaborators, 2017; Kessler and Wang, 2008). The substantial influence of genetic variation on risk for a broad range of psychiatric disorders has been established by both twin and, more recently, large-scale genomic studies (Smoller et al., 2018). Psychiatric disorders are highly polygenic, with a large proportion of heritability contributed by common variation. Many risk loci have emerged from genome-wide association studies (GWAS) of, among others, schizophrenia (SCZ), bipolar disorder (BIP), major depression (MD), and attention-deficit/hyperactivity disorder (ADHD) from the Psychiatric Genomics Consortium (PGC) and other efforts (Sullivan et al., 2018). These studies have revealed a surprising degree of genetic overlap among psychiatric disorders (Brainstorm Consortium, 2018; Cross-Disorder Group of the Psychiatric Genomics Consoritum, 2013). Elucidating the extent and biological significance of cross-disorder genetic influences has implications for psychiatric nosology, drug development, and risk prediction. In addition, characterizing the functional genomics of cross-phenotype genetic effects may reveal fundamental properties of pleiotropic loci that differentiate them from disorder-specific loci, and help identify targets for diagnostics and therapeutics.
