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.
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.
Yue W.-H.,Peking University |
Wang H.-F.,Chinese National Human Genome Center at Shanghai |
Wang H.-F.,Shanghai JiaoTong University |
Sun L.-D.,Anhui Medical University |
And 64 more authors.
Nature Genetics | Year: 2011
To identify susceptibility loci for schizophrenia, we performed a two-stage genome-wide association study (GWAS) of schizophrenia in the Han Chinese population (GWAS: 746 individuals with schizophrenia and 1,599 healthy controls; validation: 4,027 individuals with schizophrenia and 5,603 healthy controls). We identified two susceptibility loci for schizophrenia at 6p21-p22.1 (rs1233710 in an intron of ZKSCAN4, P combined = 4.76 × 10 -11, odds ratio (OR) = 0.79; rs1635 in an exon of NKAPL, P combined = 6.91 × 10 -12, OR = 0.78; rs2142731 in an intron of PGBD1, P combined = 5.14 × 10 -10, OR = 0.79) and 11p11.2 (rs11038167 near the 5ĝ€2 UTR of TSPAN18, P combined = 1.09 × 10 -11, OR = 1.29; rs11038172, P combined = 7.21 × 10 -10, OR = 1.25; rs835784, P combined = 2.73 × 10 -11, OR = 1.27). These results add to previous evidence of susceptibility loci for schizophrenia at 6p21-p22.1 in the Han Chinese population. We found that NKAPL and ZKSCAN4 were expressed in postnatal day 0 (P0) mouse brain. These findings may lead to new insights into the pathogenesis of schizophrenia. © 2011 Nature America, Inc. All rights reserved.
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.