Genetic copy number variants in sib pairs both affected with schizophrenia.
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.
Lee
Chia-Huei
CH
Department of Psychiatry, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
Liu
Chih-Min
CM
Wen
Chun-Chiang
CC
Chang
Shun-Min
SM
Hwu
Hai-Gwo
HG
D000328:Adult; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations / Q000235:genetics*; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology; D035781:Siblings