Recent studies suggest that copy number variation in the human genome is extensive and may play an important role in susceptibility to disease, including neuropsychiatric disorders such as schizophrenia and autism. The possible involvement of copy number variants (CNVs) in bipolar disorder has received little attention to date.
To determine whether large (>100,000 base pairs) and rare (found in <1% of the population) CNVs are associated with susceptibility to bipolar disorder and to compare with findings in schizophrenia.
A genome-wide survey of large, rare CNVs in a case-control sample using a high-density microarray.
The Wellcome Trust Case Control Consortium.
There were 1697 cases of bipolar disorder and 2806 nonpsychiatric controls. All participants were white UK residents.
Overall load of CNVs and presence of rare CNVs.
The burden of CNVs in bipolar disorder was not increased compared with controls and was significantly less than in schizophrenia cases. The CNVs previously implicated in the etiology of schizophrenia were not more common in cases with bipolar disorder.
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.
"Prompted by these findings, we focused on the EGR2 as a candidate gene for schizophrenia in this study. Schizophrenia can be attributed to the joint effects of multiple common variants with a small-to-modest effect on the risk (Cichon et al., 2009) and rare mutations with large effect (Grozeva et al., 2010; Kenny et al., 2014; Tarabeux et al., 2011; Walsh et al., 2008). Thus, we aimed to examine whether there are common or rare genetic variants of the EGR2 associated with schizophrenia. "
"The contribution of CNVs in the psychiatric disorders has been appreciated only recently with the implementation of array technologies that enable genome-wide determination of CNVs. Two studies of CNVs in BP reported no overall increase in CNV load in cases and found that controls had a significant excess of CNVs [Grozeva et al., 2010; McQuillin et al., 2011]. In a third study, a nominally significant increase in singleton CNVs in BP cases compared with controls was found [Zhang et al., 2009]. "
[Show abstract][Hide abstract] ABSTRACT: The current schizophrenia concept is built on experts' agreement on the matter, and it is basically rooted in the epidemiological and clinical evidence. However, the numerous and intensive attempts to find the biological underpinnings of this syndrome face almost constantly a low degree of replication of the results. We have reviewed previously published work to contribute to identify some reasons underlying that failure. The difficulty in replicating biological findings in schizophrenia may relate to the intrinsic heterogeneity among patient samples, acquired through the current diagnostic criteria. As a result, the necessary replication for any finding to be accepted as characteristic data for schizophrenia would be impeded. Therefore, a new frame based on identification of correlates of the most replicated biological anomalies in schizophrenia to date may contribute to overcome those difficulties.
The Journal of nervous and mental disease 09/2013; 201(9):744-52. DOI:10.1097/NMD.0b013e3182a21444 · 1.69 Impact Factor
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