Abstract
ObjectivesSchizophrenia (SZ) is a complex psychiatric disorder that has a strong genetic basis. Dystrobrevin-binding protein 1 (DTNBP1) is one of the genes thought to be pivotal in regulating the glutamatergic system. Studies have suggested that variations in DTNBP1 confer susceptibility to SZ and clinical symptoms. Here, we performed a two-stage independent verification study to identify polymorphisms of the DTNBP1 gene that might be associated with SZ in the Han Chinese population.MethodsIn stage 1, 14 single nucleotide polymorphisms (SNPs) were genotyped in 528 paranoid SZ patients and 528 healthy controls (HCs) using the Illumina GoldenGate assays on a BeadStation 500G Genotyping System. In stage 2, ten SNPs were genotyped in an independent sample of 1,031 SZ patients and 621 HCs using the Illumina 660k Genotyping System. Clinical symptoms were assessed using the Positive and Negative Syndrome Scale.ResultsThere was a significant association related to allele frequency, and a trend association in relation to genotype between SZ patients and HCs at rs4712253 (p = 0.03 and 0.05, respectively). These associations were not evident following Bonferroni correction (p > 0.05 for both). Haplotype association analysis revealed that only two haplotypes (GAG and GAA; rs16876575-rs9464793-rs4712253) were significantly different between SZ patients and HCs (χ2 = 4.24, 6.37, p = 0.04 and 0.01, respectively). In addition, in SZ patients there was a significant association in the rs4964793 genotype for positive symptoms, and in the rs1011313 genotype for excitement/hostility symptoms (p = 0.01 and 0.002, respectively). We found a significant association in the baseline symbol digital modalities test (SDMT), forward-digital span (DS), backward-DS, and semantic fluency between SZ patients and HCs (p < 0.05 for all). Finally, the SNP rs1011313 genotypes were associated with SDMT in SZ patients (p = 0.04).ConclusionThis study provides further evidence that SNP rs4712253 of DTNBP1 has a nominal association with SZ in the Han Chinese population. Such a genotype variation may play a role in psychopathology and cognitive function.
Highlights
Schizophrenia (SZ) is a chronic and complex mental illness, with up to 1% of the world's population being affected [1]
This study aimed to explore the association of DTNBP1 polymorphisms in patients with SZ and psychopathology and cognition in the Han Chinese population during two stages
We found no significant association in relation to genotypes or allele frequency between SZ patients and HCs at rs1011313 and rs2619539; these results were consistent with previous studies and a rs9464793 AA AG GG
Summary
Schizophrenia (SZ) is a chronic and complex mental illness, with up to 1% of the world's population being affected [1]. SZ genetic research often focuses on identifying linkage regions, candidate genes and single nucleotide polymorphisms (SNPs). A genome wide association study with a large sample size found 108 susceptibility loci associated with SZ, underscoring the complex genetic component of SZ [4]. Some previous studies have suggested that multiple individual mutations could alter genes in neurotransmitter pathways such as the glutamatergic system, which contribute to the development of SZ [5, 6]. Based on results of previous studies, some researchers believed that the neural pathway involved in DTNBP1 may constitute a potential therapeutic target for the treatment of SZ [10, 14], and suggested that DTNBP1 plays a role underlying the etiology of SZ
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