title: Genome-Wide Association Study Suggested the PTPRD Polymorphisms Were Associated With Weight Gain Effects of Atypical Antipsychotic Medications.
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.
authors.forename: Hao
authors.initials: H
authors.lastname: Yu
authors.affiliation: Peking University Sixth Hospital, Institute of Mental Health, Beijing, China; Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Center for Mental Disorders, Peking University, Beijing, China;
authors.forename: Lifang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Psychiatry of the Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, China; Henan Mental Hospital, Henan Key Lab of Biological Psychiatry, Xinxiang, Henan, China;
authors.forename: Luxian
authors.initials: L
authors.lastname: Lv
authors.affiliation: Jinzhou Kangning Hospital, Jinzhou, Liaonin, China;
authors.forename: Cuicui
authors.initials: C
authors.lastname: Ma
authors.affiliation: Hebei Mental Health Center, Baoding, Hebei, China;
authors.forename: Bo
authors.initials: B
authors.lastname: Du
authors.affiliation: Peking University Sixth Hospital, Institute of Mental Health, Beijing, China; Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Center for Mental Disorders, Peking University, Beijing, China;
authors.forename: Tianlan
authors.initials: T
authors.lastname: Lu
authors.affiliation: Jinzhou Kangning Hospital, Jinzhou, Liaonin, China;
authors.forename: Chao
authors.initials: C
authors.lastname: Jin
authors.affiliation: Peking University Sixth Hospital, Institute of Mental Health, Beijing, China; Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Center for Mental Disorders, Peking University, Beijing, China;
authors.forename: Hao
authors.initials: H
authors.lastname: Yan
authors.affiliation: Department of Psychiatry of the Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, China; Henan Mental Hospital, Henan Key Lab of Biological Psychiatry, Xinxiang, Henan, China;
authors.forename: Yongfeng
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Psychiatry of the Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, China; Henan Mental Hospital, Henan Key Lab of Biological Psychiatry, Xinxiang, Henan, China;
authors.forename: Wenqiang
authors.initials: W
authors.lastname: Li
authors.affiliation: Peking University Sixth Hospital, Institute of Mental Health, Beijing, China; Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Center for Mental Disorders, Peking University, Beijing, China;
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Ruan
authors.affiliation: Peking University Sixth Hospital, Institute of Mental Health, Beijing, China; Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Center for Mental Disorders, Peking University, Beijing, China;
authors.forename: Hongyan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Psychiatry of the Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, China; Henan Mental Hospital, Henan Key Lab of Biological Psychiatry, Xinxiang, Henan, China;
authors.forename: Hongxing
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Peking University Sixth Hospital, Institute of Mental Health, Beijing, China; Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Center for Mental Disorders, Peking University, Beijing, China;
authors.forename: Weifeng
authors.initials: W
authors.lastname: Mi
authors.affiliation: Queensland Brain Institute, University of Queensland, Brisbane, Australia; Queensland Centre for Mental Health Research, The Park - Centre for Mental Health, Wacol, Queensland, Australia;
authors.forename: Bryan
authors.initials: B
authors.lastname: Mowry
authors.affiliation: Jinzhou Kangning Hospital, Jinzhou, Liaonin, China;
authors.forename: Wenbin
authors.initials: W
authors.lastname: Ma
authors.affiliation: Hebei Mental Health Center, Baoding, Hebei, China;
authors.forename: Keqing
authors.initials: K
authors.lastname: Li
authors.affiliation: Peking University Sixth Hospital, Institute of Mental Health, Beijing, China; Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Center for Mental Disorders, Peking University, Beijing, China; Peking-Tsinghua Center for Life Sciences/PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China.
authors.forename: Dai
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Peking University Sixth Hospital, Institute of Mental Health, Beijing, China; Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Center for Mental Disorders, Peking University, Beijing, China; dryue@bjmu.edu.cn.
authors.forename: Weihua
authors.initials: W
authors.lastname: Yue
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects*; D015331:Cohort Studies; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2 / Q000235:genetics*; D012559:Schizophrenia / Q000188:drug therapy / Q000235:genetics*; D015430:Weight Gain / Q000187:drug effects / Q000235:genetics*; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; C090899:PTPRD protein, human; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2
keywords: D (PTPRD); antipsychotic-induced weight gain (AIWG); genome-wide association study; protein tyrosine phosphatase; receptor type; schizophrenia