Genome-Wide Association Study Suggested the PTPRD Polymorphisms Were Associated With Weight Gain Effects of Atypical Antipsychotic Medications.
Schizophr Bull
; 42(3): 814-23, 2016 May.
Article
em En
| MEDLINE
| ID: mdl-26656879
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Esquizofrenia
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Antipsicóticos
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Aumento de Peso
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Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores
Tipo de estudo:
Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article