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29-11-2011 | Mental health | Article

Six rare CNVs strongly linked to schizophrenia


Free abstract

MedWire News: Results from a UK study provide strong support for an association between schizophrenia and six rare copy number variants (CNVs).

"Since 2008, several specific CNVs that represent deletions or duplications of more than 1000 bp [base pairs] of DNA, have been shown to increase susceptibility to schizophrenia as well as other neurodevelopmental disorders," explain George Kirov (Cardiff University) and team.

They add: "All implicated CNVs are very rare, occurring in about 1:150 to 1:1000 individuals with schizophrenia, frequencies about 2 to 10 times higher than in controls. However, because of their rarity, the frequencies in the general population have not yet been confidently established."

To better understand the robustness and specificity of the association of these CNVs with schizophrenia, the team studied genetic data on 10,259 individuals from the UK Wellcome Trust Case Control Consortium (WTCCC) who had one of six nonpsychiatric disorders (coronary artery disease, Crohn's disease, hypertension, rheumatoid arthritis, and diabetes [Type 1 and 2]).

The team compared the frequency of nine CNVs in the WTCCC reference set with that in schizophrenia patients from nine of the largest published studies or reviews, as well as using combined data from studies that had at least 1000 schizophrenia patients and 1000 controls.

The researchers found that deletions at 1q21.1, 3q29, 15q11.2, 15q13.1 and 22q11.2 were significantly more common in schizophrenia patients compared with the WTCCC reference set, at 20/11,392 patients versus 1/10,259 controls, 9/9323 versus 0/10,259, 68/11,863 versus 40/10,259, 21/10,887 versus 4/10,259, and 35/11,400 versus 0/10,259, respectively.

The duplication at 16p11.2 was also significantly more common in schizophrenia patients than the WTCCC reference set, at 26/8590 patients versus 4/10,259 controls.

Rates of the remaining three duplications/deletions were either not significantly different between the two groups, or present at a higher rate in the WTCCC reference set.

Kirov and team conclude: "The evidence for association with schizophrenia is compelling for six rare CNV loci, while the remaining three require further replication in large studies."

They add: "Risk at these loci extends to other neurodevelopmental disorders but their involvement in common non-psychiatric disorders should also be investigated."

MedWire ( is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2011

By Mark Cowen

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