Support for the involvement of the ERBB4 gene in schizophrenia: A genetic association analysis

Cellular, animal and human studies support the involvement of aberrant NRG-ErbB signaling in the pathogenesis of schizophrenia. The aim of the present study was to examine whether genetic variation in the human ERBB4 gene is associated with susceptibility to schizophrenia. Two hundred and twenty-seven unrelated chronic inpatients with schizophrenia were enrolled in the study, and the genetic variation in the polymorphisms of the ERBB4 gene in the patients was compared with that of the control group, which consisted of 223 subjects free of psychiatric illness. The results showed that one coding-synonymous polymorphism (rs3748962, Val1065Val) was in genotypic (p = 0.0027) and allelic (p = 0.0007) association with Schizophrenia. In comparison with subjects of the rs3748962-TT type, those of the rs3748962-CT and rs3748962-CC types were at 1.74- and 2.64-fold greater risk of schizophrenia (CT vs. TT: OR = 1.71 (95% CI = 1.15-2.53), p = 0.0014; CC vs. TT: OR = 2.64 (95% CI = 1.37-5.23), p = 0.0047), which supports the hypothesis of an additive model of transmission (p = 0.0006). Furthermore, the frequency of haplotype ATC of rs3791709-rs2289086-rs3748962 was found to be significantly higher in the patients with schizophrenia than in the controls (case vs. control = 36.0% vs. 24.4%, permutation p-value = 0.0002). The findings support the involvement of the ERBB4 gene in schizophrenia in Han Chinese. (C) 2010 Elsevier Ireland Ltd. All rights reserved.