Further boost for copy number variant role in schizophrenia

Dec 20 2013

By Afsaneh Gray, medwireNews Reporter

A large study confirms that 11 previously identified copy number variants (CNVs) are likely associated with schizophrenia.

“Out of 15 previously implicated CNV loci, 11 are now strongly associated with schizophrenia from the combined results of the previous literature and our new data,” write lead researcher George Kirov (Cardiff University, UK) and colleagues in the British Journal of Psychiatry.

Furthermore, about 2.5% of schizophrenia patients were found to carry a large, detectable CNV at one of the investigated loci, compared with just 0.9% of controls. The authors suggest that given this, and the fact that a number of the individual pathogenic CNVs are also associated with diseases such as epilepsy and congenital heart disease, routine CNV screening may be clinically appropriate.

Data on 6558 people with treatment-resistant schizophrenia were obtained from anonymized blood samples. A further 571 patients with clinically diagnosed schizophrenia were recruited from community, inpatient, and voluntary sector mental health services in the UK. For a control group (n=6316), the researchers used publicly available data from the dbGAP database. A total of 91.4% of samples that passed quality control were from individuals of European descent.

Higher rates of CNVs previously implicated in schizophrenia were found among the patients for 13 of the 15 investigated loci. The association was particularly strong for duplications at chromosome 16p11.2, and at the AS/PWS critical region, and for deletions at 22q11.2, 1q21.1, and 15q11.2, and of the NRXN1 gene.

Questions have been raised about the association of two of the loci investigated in the study with schizophrenia: deletions at chromosome 15q11.2 and duplications at 16p13.11. However, the results supported their association and, when combined with results from previous studies, strengthened their statistical significance by several orders of magnitude.

Four of the loci did not surpass the significance threshold: duplications at VIPR2, and deletions at distal 16p11.2, 17p12, and 17q12.

“The robust identification of 11 relatively high penetrance risk alleles for schizophrenia… offers promise for biological research aimed at developing animal and cellular models for the identification of novel disease mechanisms and drug targets,” Kirov and colleagues conclude.

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