Genome-Wide Association Study Suggested the PTPRD Polymorphisms Were   Associated With Weight Gain Effects of Atypical Antipsychotic   Medications

doi:10.1093/schbul/sbv179

CORC > 北京大学 > 生命科学学院

	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 ; Yue, Weihua
刊名	SCHIZOPHRENIA BULLETIN
	2016
关键词	schizophrenia antipsychotic-induced weight gain (AIWG) genome-wide association study protein tyrosine phosphatase, receptor type, D (PTPRD) CHRONIC-SCHIZOPHRENIA COMMON VARIANTS HUMAN BRAIN BODY-MASS GENE POPULATION OBESITY PHARMACOGENETICS DISORDERS OSBPL10
DOI	10.1093/schbul/sbv179
英文摘要	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.; National Natural Science Foundation of China [81222017, 91232305, 81361120395, 81221002]; National Key Technology R&D Program of China [2015BAI13B01, 2012BAI01B06]; Program for New Century Excellent Talents in University [NCET-12-0008]; National High Technology Research and Development Program of China [2008AA02Z401, 2009AA022702]; SCI(E); PubMed; SSCI; ARTICLE; dryue@bjmu.edu.cn; 3; 814-823; 42
语种	中文
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/435925]
专题	生命科学学院
推荐引用方式 GB/T 7714	Yu, Hao,Wang, Lifang,Lv, Luxian,et al. Genome-Wide Association Study Suggested the PTPRD Polymorphisms Were Associated With Weight Gain Effects of Atypical Antipsychotic Medications[J]. SCHIZOPHRENIA BULLETIN,2016.
APA	Yu, Hao.,Wang, Lifang.,Lv, Luxian.,Ma, Cuicui.,Du, Bo.,...&Yue, Weihua.(2016).Genome-Wide Association Study Suggested the PTPRD Polymorphisms Were Associated With Weight Gain Effects of Atypical Antipsychotic Medications.SCHIZOPHRENIA BULLETIN.
MLA	Yu, Hao,et al."Genome-Wide Association Study Suggested the PTPRD Polymorphisms Were Associated With Weight Gain Effects of Atypical Antipsychotic Medications".SCHIZOPHRENIA BULLETIN (2016).