UMMS Affiliation

Department of Psychiatry

Publication Date

2020-05-25

Document Type

Article

Disciplines

Amino Acids, Peptides, and Proteins | Cognitive Neuroscience | Molecular and Cellular Neuroscience | Nucleic Acids, Nucleotides, and Nucleosides | Psychiatry | Psychiatry and Psychology

Abstract

Objectives: Schizophrenia (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.

Methods: In 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.

Results: There 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 (chi(2) = 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).

Conclusion: This 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.

Keywords

DTNBP1, cognition, polymorphism, psychotic symptoms, schizophrenia

Rights and Permissions

Copyright © 2020 Yang, Zhang, Guo, Zhang, Yu, Liu, Su, Shao, Song, Zhang, Ding, Lu, Liu, Li, Yue, Fan, Yang and Lv. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

DOI of Published Version

10.3389/fpsyt.2020.00446

Source

Yang Y, Zhang L, Guo D, Zhang L, Yu H, Liu Q, Su X, Shao M, Song M, Zhang Y, Ding M, Lu Y, Liu B, Li W, Yue W, Fan X, Yang G, Lv L. Association of DTNBP1 With Schizophrenia: Findings From Two Independent Samples of Han Chinese Population. Front Psychiatry. 2020 May 25;11:446. doi: 10.3389/fpsyt.2020.00446. PMID: 32581860; PMCID: PMC7286384. Link to article on publisher's site

Journal/Book/Conference Title

Frontiers in psychiatry

Comments

Full author list omitted for brevity. For the full list of authors, see article.

Related Resources

Link to Article in PubMed

PubMed ID

32581860

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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