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Jinzhou, China

Chen Y.,Peking University | Tian L.,Peking University | Zhang F.,Peking University | Liu C.,Peking University | And 15 more authors.
Psychiatry Research | Year: 2013

Myosin Vb (. MYO5B) has recently been implicated in the etiology of bipolar disorder in a genome-wide association study (GWAS). This gene is involved in amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor subunit glutamate receptor 1 (GluR1) recycling and plays an important role in the primary excitatory neurotransmission. Dysfunction of the brain glutamate system has been postulated to be involved in the pathophysiology in schizophrenia. To further investigate the association between MYO5B polymorphisms and schizophrenia, we genotyped nine single nucleotide polymorphisms (SNPs) in an independent sample of 1463 individuals with schizophrenia and 1563 healthy control subjects, and detected three SNPs and two haplotype blocks which displayed significant association with schizophrenia. This association was further strengthened by the results of meta-analysis. Our data strongly supported that the MYO5B gene might be associated with schizophrenia in the Chinese Han population and they have implications for understanding the glutamate hypothesis of schizophrenia. © 2013 Elsevier Ireland Ltd.

Dong L.,Peking University | Dong L.,Min Of Health And National Clinical Research Centerfor Mental Disorders | Yan H.,Peking University | Yan H.,Min Of Health And National Clinical Research Centerfor Mental Disorders | And 37 more authors.
Pharmacological Research | Year: 2015

The ataxin-2 binding protein 1 (A2BP1) gene is reported to be one of the susceptibility genes in schizophrenia, autism, and obesity. The aim of this study was to explore the association of A2BP1 gene polymorphisms with antipsychotic induced weight gain (AIWG) in Chinese Han population. Three hundred and twenty-eight patients with schizophrenia were followed-up for an 8-week period of treatment with olanzapine. The fasting weights of 328 patients were measured before and after the 8-week course of treatment. Four single nucleotide polymorphisms (SNPs: rs8048076, rs1478697, rs10500331, and rs4786847) of the A2BP1 gene were genotyped by polymerase chain reaction (PCR). We analyzed putative association of A2BP1 polymorphisms with AIWG of olanzapine using linear regression analysis and found that SNP rs1478697 was significantly associated with AIWG caused by olanzapine (p = 0.0012; Bonferroni corrected p = 0.0048). The association was replicated in another independent sample including 208 first-episode and drug-naïve patients presenting with schizophrenia after a 4-week treatment with olanzapine (p = 0.0092; Bonferroni corrected p = 0.0368; meta p = 5.33 × 10-5). To explore the biological plausibility of A2BP1 in the pathogenesis of AIWG, we made expression analyses and eQTL analyses; these analyses showed that A2BP1 was highly expressed in whole brain tissues using the HBT database, and that rs1478697 has an expression quantitative trait locus effect in human cerebellar cortex tissues using the BRAINEAC database (p = 2.50E-04). In conclusion, the rs1478697 in A2BP1 may be associated with AIWG induced by 8-week treatment with olanzapine. © 2015 Elsevier Ltd. All rights reserved.

Wang F.,Peking University | Wang F.,Capital Medical University | Mi W.,Peking University | Ma W.,Jinzhou Kangning Hospital | And 15 more authors.
Pharmacogenomics | Year: 2015

Aim: We carried out a pharmacogenomic study in order to identify susceptible genes for antipsychotics induced weight gain within the Chinese Han population. Materials & methods: We enrolled 216 patients with schizophrenia in our study. All of them underwent risperidone monotherapy, and fulfilled 4-week follow-up. Weight gain was measured before treatment and 4 weeks later. Seven hundred and sixty-eight SNPs from 85 genes were calculated for association with weight gain percentage. Results: Fifty-seven SNPs located at 16 genes with a p-value less than 0.05.4 SNPs located on serotonin transporter gene (solute carrier family 6, member 4, SLC6A4) remained significant after multitest correction (rs3813034, p = 0.000357, q = 0.08, rs1042173, rs4325622, rs9303628, p = 0.000451, q = 0.08). Conclusion: SLC6A4 might be susceptible gene for risperidone-induced weight gain within the Chinese Han population. © 2015 Future Medicine Ltd.

Zheng F.,Peking University | Zhang Y.,Peking University | Zhang Y.,China Aerospace Science and Technology Corporation | Xie W.,Capital Medical University | And 22 more authors.
Schizophrenia Research | Year: 2014

CACNA1C (12p13.3) has been implicated as a susceptibility gene for schizophrenia by several replicated genome wide association studies. While these results have been consistent among studies in European populations, the findings in East Asian populations have varied. To test whether CACNA1C is a risk gene for schizophrenia, we conducted a case-control study in 5897 schizophrenic patients and 6323 healthy control subjects selected from Han Chinese population. Our study replicated the positive associations of rs1006737 (P=0.0108, OR=1.16, 95% CI: 1.03-1.29) and rs1024582 (P=0.0062, OR=1.18, 95% CI: 1.05-1.33), and identified a novel risk locus, rs2007044 (P=0.0053, OR=1.08, 95% CI: 1.02-1.14). A meta-analysis of rs1006737 combining our study and previous studies was conducted in a total of 8222 schizophrenia cases and 24,661 healthy controls. In the meta-analysis, the association between rs1006737 and schizophrenia remained significant (OR=1.14, 95% CI: 1.07-1.22, P=0.0001). Stratified analysis showed no heterogeneity between East Asian and European ancestries (χ2[1]=0.07, P=0.795), and the difference in pooled ORs between ancestries was not significant (Z=0.25, P=0.801). Our results provide further support for associations of rs1006737 and rs1024582 with schizophrenia, identify a new risk locus rs2007044 in a Han Chinese population, and further establish CACNA1C as an important susceptibility gene for the disease across world populations. © 2013.

Yu H.,Peking University | Yu H.,Tsinghua University | Wang L.,Peking University | Lv L.,Xinxiang Medical University | And 22 more authors.
Schizophrenia Bulletin | Year: 2016

Background: Antipsychotic-induced weight gain (AIWG) is a serious concern in therapy with antipsychotic medications. To identify single nucleotide polymorphisms (SNPs) associated with AIWG, we conducted a genome-wide association study (GWAS) for antipsychotic treatment. Methods: The discovery cohort consisted of 534 patients with schizophrenia, who underwent 8-week treatment with antipsychotics and were genotyped using the Illumina Human 610-Quad BeadChip. The independent replication cohort consisted of 547 patients with schizophrenia, treated with similar antipsychotics, and genotyped using the Sequenom MassARRAY platform. Two hundred and thirty-six drug-naive patients treated with risperidone or quetiapine were analyzed independently. Additionally, we conducted pathway and expression analyses using several public bioinformatics databases. Results: After correction for age and gender, the top 2 genome-wide significant SNPs with AIWG were located in the PTPRD gene (protein tyrosine phosphatase, receptor type D, 9p24-p23; rs10977144, P GWAS = 9.26E-09; rs10977154, P GWAS = 4.53E-08). The third most significant SNP was in the GFPT2 gene (glutamine-fructose-6-phosphate amidotransferase 2, 5q35.3; rs12386481, P GWAS = 1.98E-07). These results were validated in the replication cohort (rs10977144, P Replication = 4.30E-03; rs10977154, P Replication = 6.33E-03; rs12386481, P Replication =7.65E-03). These results were also verified in those patients initially exposed to risperidone and quetiapine (rs10977144, P = 1.97E-05; rs10977154, P = 2.04E-05; rs12386481, P = 1.97E-04). Pathway analyses showed that AIWG may involve in multiple pathways related to metabolic processes. Moreover, PTPRD mRNA might be highly expressed in brain regions, and the SNPs (rs10977144, rs1097154) also showed significant expression quantitative trait locus effects. Conclusions: Our findings indicate that PTPRD polymorphisms might modulate AIWG. © The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.

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