An immune involvement is another longstanding hypothesis of schizophrenia, based on various lines of evidence (Carter et al., 2014; Patterson, 2009), including an association with human leukocyte antigen (HLA) status (McGuffin, 1979). GWAS studies have confirmed that the MHC locus on chromosome 6, which encodes HLA and other immune genes (as well as some genes not related to immune function), is associated with the disorder (Corvin and Morris, 2014; McGuffin and Power, 2013; Purcell et al., 2009; Schizophrenia Working Group of the Psychiatric Genomics Consortium, 2014). There is also evidence for involvement of immune genes located outside the MHC region (Schizophrenia Working Group of the Psychiatric Genomics Consortium, 2014). The MHC locus is probably one of the sources of genetic difference between schizophrenia and bipolar disorder, since the latter shows no association (Andreassen et al., 2013). Intriguingly, the discovery that MHC genes also have functions in brain development and in glutamate receptor signalling and synaptic plasticity (Fourgeaud et al., 2010; Lee et al., 2014) provides a potential link between MHC- and NMDAR-related aspects of the genetic aetiology of schizophrenia (McAllister, 2014).
