Rare Copy Number Variants<subtitle>A Point of Rarity in Genetic Risk for Bipolar Disorder and Schizophrenia</subtitle><alt-title>Rare Copy Number Variants</alt-title>

Abstract

Schizophrenia and bipolar disorder differ with respect to CNV burden in general and association with specific CNVs in particular. Our data are consistent with the possibility that possession of large, rare deletions may modify the phenotype in those at risk of psychosis: those possessing such events are more likely to be diagnosed as having schizophrenia, and those without them are more likely to be diagnosed as having bipolar disorder.

Investigating relationships between cortical thickness and cognitive performance in patients with schizophrenia and healthy adults

“…Also consistent with more extensive findings or a greater intensity in schizophrenia are the recent studies that find some of the disease specificity to schizophrenia to be associated with structural genomic variations, such as copy number variations (CNVs) (Grozeva et al, 2010;Sebat et al, 2009;Stefansson et al, 2008). Also, differences in exposure to biological environmental stressors such as viruses and obstetrical complications could affect the common genes differently, leading to differences in degree of structural abnormalities.…”

A genetic model for neurodevelopmental disease

“…Studies of adults with schizophrenia and epilepsy demonstrate lower diagnostic yields of ~5% [11,12,18,23,24]. For other neurodevelopmental conditions there is either conflicting evidence for increased CNV burden, such as for bipolar disorder [25,26], or no evidence, as for Tourette's syndrome and dyslexia [19,20,27]. In all cases burden statistics are more significant when considering de novo events exclusively [15,18,21,22,26].…”

Neurodevelopment, GABA System Dysfunction, and Schizophrenia

“…Furthermore, it also appears that rare copy number variants with potentially large effect sizes might have an important role in predisposing to schizophrenia. These deletions or duplications of chromosomal regions often span multiple genes and can either increase risk or protect from diagnosis, presumably by altering the 'dosing' of the genes contained within the variant region (Grozeva et al, 2010;International Schizophrenia C, 2008;Stefansson et al, 2008). For example, 22q11 hemideletion is associated with high rates of schizophrenia (Gothelf et al, 1997;Karayiorgou et al, 2010;Murphy et al, 1999), whereas 22q11 duplication may protect against schizophrenia diagnosis (Rees et al, 2014), suggesting that expression levels of specific genes are critical to normal and pathological brain development.…”