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Research

Genetic copy number variants in sib pairs both affected with schizophrenia

Chia-Huei Lee , Chih-Min Liu , Chun-Chiang Wen , Shun-Min Chang and Hai-Gwo Hwu

Journal of Biomedical Science 2010, 17:2doi:10.1186/1423-0127-17-2

Published:	11 January 2010

Abstract (provisional)

Background

Schizophrenia is a complex disorder with involvement of multiple genes.

Methods

In this study, genome-wide screening for DNA copy-number variations (CNVs) was conducted for ten pairs, a total of 20 cases, of affected siblings using oligonucleotide array-based CGH.

Results

We found negative symptoms were significantly more severe (p < 0.05) in the subgroup that harbored more genetic imbalance (n 13, n = number of CNV-disrupted genes) as compared with the subgroup with fewer CNVs (n 6), indicating that the degree of genetic imbalance may influence the severity of the negative symptoms of schizophrenia. Four central nervous system (CNS) related genes including CCAAT/enhancer binding protein, delta (CEBPD, 8q11.21), retinoid X receptor, alpha (RXRA, 9q34.2), LIM homeobox protein 5 (LHX5, 12q24.13) and serine/threonine kinase 11 (STK11, 19p13.3) are recurrently (incidence 16.7%) disrupted by CNVs. Two genes, PVR (poliovirus receptor) and BU678720, are concordantly deleted in one and two, respectively, pairs of co-affected siblings. However, we did not find a significant association of this BU678720 deletion and schizophrenia in a large case-control sample.

Conclusions

We conclude that the high genetic loading of CNVs may be the underlying cause of negative symptoms of schizophrenia, and the CNS-related genes revealed by this study warrant further investigation.