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.
Lu
Chao-Lin
CL
Psychiatric Division, Hualien Armed Forces General Hospital, Hualien, Taiwan, ROC.
Wang
Ying-Chieh
YC
Chen
Jen-Yeu
JY
Lai
I-Ching
IC
Liou
Ying-Jay
YJ
D000328:Adult; D044466:Asian People / Q000208:ethnology / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D066247:Receptor, ErbB-4; D012559:Schizophrenia / Q000235:genetics*; D013624:Taiwan
C587689:ERBB4 protein, human; D066246:ErbB Receptors; D066247:Receptor, ErbB-4