Genetic overlap between autism, schizophrenia and bipolar disorder

Abstract

There is strong evidence that genetic factors make substantial contributions to the etiology of autism, schizophrenia and bipolar disorders, with heritability estimates being at least 80% for each. These illnesses have complex inheritance, with multiple genetic and environmental factors influencing disease risk; however, in psychiatry, complex genetics is further compounded by phenotypic complexity. Autism, schizophrenia and bipolar disorder are effectively syndromic constellations of symptoms that define groups of patients with broadly similar outcomes and responses to treatment. As such the diagnostic categories are likely to be heterogeneous and the boundaries between them somewhat arbitrary. Recent applications of whole-genome technologies have discovered rare copy number variants and common single-nucleotide polymorphisms that are associated with risk of developing these disorders. Furthermore, these studies have shown an overlap between the genetic loci and even alleles that predispose to the different phenotypes. The findings have several implications. First, they show that copy number variations are likely to be important risk factors for autism and schizophrenia, whereas common single-nucleotide polymorphism alleles have a role in all disorders. Second, they imply that there are specific genetic loci and alleles that increase an individual's risk of developing any of these disorders. Finally, the findings suggest that some of the specific genetic loci implicated so far encode proteins, such as neurexins and neuroligins, that function in synaptic development and plasticity, and therefore may represent a common biological pathway for these disorders.

Neuronal cell adhesion genes

“…26). The studies performed by our group and Wang and colleagues only investigated common SNP variation and there is increasing realization of the potential importance of rare, highly penetrant structural variation in the aetiology of neurodevelopmental brain disorders.…”

Autistic and schizotypal traits and global functioning in bipolar I disorder

“…This complex condition is often exacerbated by the presence of one or more comorbid conditions, in addition to a number of clinical factors such long duration of illness (Altamura et al, 2015;Altamura et al, 2010). While BD, schizophrenia spectrum disorders (SSD) and autism spectrum disorders (ASD) are considered distinct conditions, there is evidence for an overlap between BD and SSD (Altamura, Buoli, & Pozzoli, 2014;Carroll & Owen, 2009;Moller, 2003), as well as between ASD and BD (Carroll & Owen, 2009;Stahlberg, Soderstrom, Rastam, & Gillberg, 2004). Indeed, BD has a number of genetic, symptomatological and epidemiological overlaps with SSD (Laursen, Agerbo, & Pedersen, 2009;Lichtenstein et al, 2009;Murray et al, 2004), and psychosis has been recognised as an important dimension in the psychopathology of BD (van Os & Kapur, 2009).…”

The Synaptic Proteins β-Neurexin and Neuroligin Synergize With Extracellular Matrix-Binding Vascular Endothelial Growth Factor A During Zebrafish Vascular Development

“…In the last years, several reports have presented about the involvement of different mutations of NRXNs and NLGNs in autism and other human cognitive diseases. 4 In mice, knocking-out NLGNs 1-3 or the 3 α-forms of NRXN reveal a role of these molecules in the fine modulation of synaptic activity. 5,6 Notably, experimental data about the in vivo function of β-NRXNs in knockout mice are still missing.…”