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

ABSTRACT: 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.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.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.Our findings indicate that PTPRD polymorphisms might modulate AIWG.

SUBMITTER: Yu H

PROVIDER: S-EPMC4838100 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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

Yu Hao H Wang Lifang L Lv Luxian L Ma Cuicui C Du Bo B Lu Tianlan T Jin Chao C Yan Hao H Yang Yongfeng Y Li Wenqiang W Ruan Yanyan Y Zhang Hongyan H Zhang Hongxing H Mi Weifeng W Mowry Bryan B Ma Wenbin W Li Keqing K Zhang Dai D Yue Weihua W

Schizophrenia bulletin 20151209 3

<h4>Background</h4>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.<h4>Methods</h4>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 replicatio ...[more]

PMID: 26656879

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Project description:Studies have found that antipsychotics and antidepressants are associated with weight gain and obesity, particularly among women and some minority groups. Incarcerated populations (also referred to as offenders, prisoners or inmates) have a high prevalence of mental health problems and 15 % of offenders have been prescribed medications. Despite rates of antidepressant and antipsychotic use, investigations of weight gain and obesity in regard to these agents seldom have included offenders.This retrospective descriptive study (2005-2011) was conducted with a Department of Corrections in the east south central United States to investigate the relationship between antidepressant and antipsychotic agents, weight gain, obesity and race or gender differences. We sampled adult offenders who had an active record, at least two weight observations and height data. Offenders were classified into one of four mutually exclusive groups depending upon the type of medication they were prescribed: antidepressants, antipsychotics, other medications or no pharmacotherapy.The sample population for this study was 2728, which was 25.2 % of the total population. The population not on pharmacotherapy had the lowest baseline obesity rate (31.7 %) compared to offenders prescribed antipsychotics (43.6 %), antidepressants (43.6 %) or other medications (45.1 %). Offenders who were prescribed antidepressants or antipsychotics gained weight that was significantly different from zero, p?<?.001 and p?=?.019, respectively. Women in the antidepressant group gained 6.4 kg compared to 2.0 kg for men, which was significant (p?=?.007). Although women in the antipsychotic group gained 8.8 kg compared to 1.6 kg for men, the finding was not significant (p?=?.122). Surprisingly, there were no significant differences in weight gain between African Americans and Whites in regard to antidepressants (p?=?.336) or antipsychotic agents (p?=?.335).This study found that women and men offenders prescribed antidepressant or antipsychotic agents gained weight during their incarceration. Women prescribed antidepressants gained significantly more weight than men. However, there was no significant difference in weight gain between African Americans and Whites. Results suggest further investigation is needed to understand the effect of medication history, metabolic syndrome and to explain gender disparities.

Project description:RationaleWeight gain is a frequent side effect of treatment with SGAs (second-generation antipsychotics) and a leading cause for nonadherence. Several candidate genes have been identified that could influence the amount of AIWG (antipsychotic-induced weight gain). The polymorphism rs17782313 near the MC4R (human melanocortin 4 receptor gene) was strongly associated with obesity in a large scale GWAS (genome wide association study), yet previous studies investigating its impact on AIWG did not lead to a definite conclusion regarding its effect. In particular, they were all relatively short and had a naturalistic design.ObjectiveWe therefore examined the influence of the rs17782313 polymorphism on SGA-related weight gain.MethodsParticipants of a multicenter randomized, controlled, double-blind study comparing two treatment strategies in individuals with schizophrenia or schizoaffective disorder were genotyped using a rapid-cycle polymerase chain reaction. Up to 252 individuals completed the first 2 weeks (phase I), 212 the entire 8 weeks (hence 'completers'). Patients received either amisulpride or olanzapine or both consecutively. Thirty-seven had their first episode. Weight gain occurring in different genotypes was statistically compared and confounding factors were adjusted by stepwise multiple linear regression. A correction for multiple testing was included.ResultsWithin 212 'completers', carriers of the C allele had a higher absolute weight gain than those homozygous for the T allele (2.6 kg vs. 1.2 kg), though this observation was not significant (P = 0.063). In the amisulpride subpopulation, this association appeared stronger and reached significance (2.5 kg vs. 0.7 kg, P = 0.043), though failed to remain significant after correction for multiple testing. A stepwise multiple linear regression showed a significant association in both the whole study population (P < 0.001) and the amisulpride subpopulation (P < 0.001).ConclusionOur results indicate that the rs17782313 polymorphism might influence antipsychotic-induced weight gain and therefore confirm some of the earlier conclusions.

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

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

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