CNVs in neuropsychiatric disorders

Abstract

Over the last few years at least 11 copy number variations (CNVs) have been shown convincingly to increase risk to developing schizophrenia: deletions at 1q21.1, NRXN1, 3q29, 15q11.2, 15q13.3 and 22q11.2, and duplications at 1q21.1, 7q11.23, 15q11.2-q13.1, 16p13.1 and proximal 16p11.2. They are very rare, found cumulatively in 2.4% of patients with schizophrenia and in only 0.5% of controls. They all increase risk for other neurodevelopmental disorders, such as developmental delay and autism spectrum disorders, where they are found at higher rates (3.3%). Their involvement in bipolar affective disorder is much less prominent. All of them affect multiple genes (apart from NRXN1) and cause substantial increases in risk to develop schizophrenia (odds ratios of 2 to over 50). Their penetrance for any neurodevelopmental disorder is high, from ∼10% to nearly 100%. Carriers of these CNVs display cognitive deficits, even when free of neuropsychiatric disorders.