Gender-Specific Associations between CHGB Genetic Variants and Schizophrenia in a Korean Population

Abstract

Purpose: Schizophrenia is a devastating mental disorder and is known to be affected by genetic factors. The chromogranin B (CHGB), a member of the chromogranin gene family, has been proposed as a candidate gene associated with the risk of schizophrenia. The secretory pathway for peptide hormones and neuropeptides in the brain is regulated by chromogranin proteins. The aim of this study was to investigate the potential associations between genetic variants of CHGB and schizophrenia susceptibility. Materials and Methods: In the current study, 15 single nucleotide polymorphisms of CHGB were genotyped in 310 schizophrenia patients and 604 healthy controls. Results: Statistical analysis revealed that two genetic variants (non-synonymous rs910122; rs2821 in 3'-untranslated region) were associated with schizophrenia [minimum p= 0.002; odds ratio (OR)= 0.72], even after correction for multiple testing (pcorr= 0.02). Since schizophrenia is known to be differentially expressed between sexes, additional analysis for sex was performed. As a result, these two genetic variants (rs910122 and rs2821) and a haplotype (ht3) showed significant associations with schizophrenia in male subjects (pcorr= 0.02; OR= 0.64), whereas the significance disappeared in female subjects (p> 0.05). Conclusion: Although this study has limitations including a small number of samples and lack of functional study, our results suggest that genetic variants of CHGB may have sex-specific effects on the risk of schizophrenia and provide useful preliminary information for further study.