Genome-wide association study suggested the PTPRD polymorphisms were associated with weight gain effects of atypical antipsychotic medications

Yu, Hao, Wang, Lifang, Lv, Luxian, Ma, Cuicui, Du, Bo, Lu, Tianlan, Jin, Chao, Yan, Hao, Yang, Yongfeng, Li, Wenqiang, Ruan, Yanyan, Zhang, Hongyan, Zhang, Hongxing, Mi, Weifeng, Mowry, Bryan, Ma, Wenbin, Li, Keqing, Zhang, Dai and Yue, Weihua (2015) Genome-wide association study suggested the PTPRD polymorphisms were associated with weight gain effects of atypical antipsychotic medications. Schizophrenia Bulletin, 42 3: 814-823. doi:10.1093/schbul/sbv179


Author Yu, Hao
Wang, Lifang
Lv, Luxian
Ma, Cuicui
Du, Bo
Lu, Tianlan
Jin, Chao
Yan, Hao
Yang, Yongfeng
Li, Wenqiang
Ruan, Yanyan
Zhang, Hongyan
Zhang, Hongxing
Mi, Weifeng
Mowry, Bryan
Ma, Wenbin
Li, Keqing
Zhang, Dai
Yue, Weihua
Title Genome-wide association study suggested the PTPRD polymorphisms were associated with weight gain effects of atypical antipsychotic medications
Journal name Schizophrenia Bulletin   Check publisher's open access policy
ISSN 0586-7614
1745-1701
Publication date 2015-01-01
Year available 2015
Sub-type Article (original research)
DOI 10.1093/schbul/sbv179
Open Access Status Not Open Access
Volume 42
Issue 3
Start page 814
End page 823
Total pages 10
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Language eng
Formatted abstract
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.
Keyword Schizophrenia
Antipsychotic-induced weight gain (AIWG)
Genome-wide association study
Protein tyrosine phosphatase
Receptor type
D (PTPRD)
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2016 Collection
 
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Created: Tue, 05 Apr 2016, 02:47:59 EST by Susan Day on behalf of Queensland Brain Institute