Abstract

BackgroundSchizophrenia (SZ) is a complex polygenic psychiatric disorder caused in part by abnormal dopamine levels. Cerebral dopamine neurotrophic factor (CDNF) 2 is known to protect and repair the dopaminergic system. Dopamine dysfunction is one of the pathogenesis of SZ. However, the relationship between CDNF2 and SZ has not been previously investigated. We speculated that CDNF2 may be a susceptibility factor for SZ.MethodsTo address this issue, we carried out a study to investigate the association between CDNF2 and SZ in the total sample 1371 (670 SZ patients and 701 healthy controls) Han Chinese population. Stage 1 included 528 SZ patients and 528 healthy controls; and stage 2 included 142 SZ patients and 173 healthy controls. The allele and genotype frequencies of five single nucleotide polymorphisms (rs2577074, rs2577075, rs2249810, rs6506891, and rs2118343) of CDNF2 were compared between patients and controls.ResultsWe found a significant association in allele and genotype frequencies between the two groups at rs2249810 (χ2 = 4.38 and 6.45, respectively; P = 0.03 and 0.04, respectively). An association was also observed in males at rs2249810 (χ2 = 8.76; P = 0.03). Haplotype TGATC differed between SZ and controls in stage 2 samples (χ2 = 6.38; P = 0.01), and rs2118343 genotypes were associated with negative factor scores (F = 4.396; P = 0.01).ConclusionsThese results suggest that rs2249810 and haplotype TGATC of CDNF2 are an SZ susceptibility locus and factor, respectively, and that rs2118343 genotypes are associated with negative symptoms of SZ in the Han Chinese population.

Highlights

  • Schizophrenia (SZ) is a complex polygenic psychiatric disorder caused in part by abnormal dopamine levels

  • To identify allelic variants of the CDNF2 gene that are associated with SZ, we analyzed two sets of samples

  • There were no significant differences in genotype and allele frequencies between SZ and controls at five single nucleotide polymorphisms (SNPs) in stage 1 samples (P > 0.05, Table 1), even after subdividing by gender and Family mental health history (FH) (P > 0.05)

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Summary

Introduction

Schizophrenia (SZ) is a complex polygenic psychiatric disorder caused in part by abnormal dopamine levels. Cerebral dopamine neurotrophic factor (CDNF) 2 is known to protect and repair the dopaminergic system. Neurotrophic factors, such as brain-derived neurotrophic factor (BDNF), nerve growth factor, glial cell line-derived neurotrophic factor, and cerebral dopamine neurotrophic factor (CDNF), can repair and protect the dopaminergic system. We speculated that CDNF is a susceptibility factor for SZ. We tested this hypothesis by examining CDNF single nucleotide polymorphisms (SNPs) in two study stages with independent sample sets

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