Genetic validation study of protein tyrosine phosphatase receptor type D (PTPRD) gene variants and risk for antipsychotic-induced weight gain

Malgorzata Maciukiewicz, Ilona Gorbovskaya, Arun K. Tiwari, Clement C. Zai, Natalie Freeman, Herbert Y Meltzer, James L. Kennedy, Daniel J. Müller*

*Corresponding author for this work

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Schizophrenia is a severe, debilitating disorder with a lifetime prevalence of 1% irrespective of gender or ethnicity and is typically treated with antipsychotic drugs. Antipsychotic-induced weight gain (AIWG) is a leading factor of patient non-compliance and has previously been shown to increase the risk of type 2 diabetes, metabolic syndrome, and cardiovascular events. The current study intends to replicate findings from a recent genome-wide association study in Han-Chinese patients implicating two gene variants (rs10977144 and rs10977154) of the protein tyrosine phosphatase receptor type D (PTPRD) in antipsychotic-induced weight gain (AIWG). We investigated a sample of European and African American ancestry (n = 201) and calculated percentage of weight change using linear regression corrected for type of antipsychotics, duration of treatment and principal components from ancestry checks. As secondary goal, we investigated additional gene variants of PTPRD previously not associated with AIWG. We found no association with rs10977144 and rs10977154. However, we found nominally significant results between PTPRD and AIWG with rs73398242 in Europeans (BETA = − 0.267, p = 0.002) and rs13294608 in African Americans (BETA = 0.423, p = 0.003). According to Haploreg, both SNPs are histone marks for enhancers and promoters across various brain regions including the cingulate gyrus and dorsolateral prefrontal cortex. In summary, our results tentatively suggest that PTPRD might be associated with AIWG although different SNPS might be involved in different ethnic groups.

Original languageEnglish (US)
Pages (from-to)27-33
Number of pages7
JournalJournal of Neural Transmission
Volume126
Issue number1
DOIs
StatePublished - Jan 21 2019

Fingerprint

Class 2 Receptor-Like Protein Tyrosine Phosphatases
Validation Studies
Antipsychotic Agents
Weight Gain
Genes
African Americans
Histone Code
Metabolic Syndrome X
Protein Tyrosine Phosphatases
Genome-Wide Association Study
Gyrus Cinguli
Patient Compliance
Prefrontal Cortex
Ethnic Groups
Type 2 Diabetes Mellitus
Single Nucleotide Polymorphism
Linear Models
Schizophrenia
Weights and Measures

Keywords

  • Antipsychotic-induced weight gain (AIWG)
  • Antipsychotics
  • PTPRD
  • Pharmacogenetics

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

Maciukiewicz, Malgorzata ; Gorbovskaya, Ilona ; Tiwari, Arun K. ; Zai, Clement C. ; Freeman, Natalie ; Meltzer, Herbert Y ; Kennedy, James L. ; Müller, Daniel J. / Genetic validation study of protein tyrosine phosphatase receptor type D (PTPRD) gene variants and risk for antipsychotic-induced weight gain. In: Journal of Neural Transmission. 2019 ; Vol. 126, No. 1. pp. 27-33.
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abstract = "Schizophrenia is a severe, debilitating disorder with a lifetime prevalence of 1{\%} irrespective of gender or ethnicity and is typically treated with antipsychotic drugs. Antipsychotic-induced weight gain (AIWG) is a leading factor of patient non-compliance and has previously been shown to increase the risk of type 2 diabetes, metabolic syndrome, and cardiovascular events. The current study intends to replicate findings from a recent genome-wide association study in Han-Chinese patients implicating two gene variants (rs10977144 and rs10977154) of the protein tyrosine phosphatase receptor type D (PTPRD) in antipsychotic-induced weight gain (AIWG). We investigated a sample of European and African American ancestry (n = 201) and calculated percentage of weight change using linear regression corrected for type of antipsychotics, duration of treatment and principal components from ancestry checks. As secondary goal, we investigated additional gene variants of PTPRD previously not associated with AIWG. We found no association with rs10977144 and rs10977154. However, we found nominally significant results between PTPRD and AIWG with rs73398242 in Europeans (BETA = − 0.267, p = 0.002) and rs13294608 in African Americans (BETA = 0.423, p = 0.003). According to Haploreg, both SNPs are histone marks for enhancers and promoters across various brain regions including the cingulate gyrus and dorsolateral prefrontal cortex. In summary, our results tentatively suggest that PTPRD might be associated with AIWG although different SNPS might be involved in different ethnic groups.",
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Genetic validation study of protein tyrosine phosphatase receptor type D (PTPRD) gene variants and risk for antipsychotic-induced weight gain. / Maciukiewicz, Malgorzata; Gorbovskaya, Ilona; Tiwari, Arun K.; Zai, Clement C.; Freeman, Natalie; Meltzer, Herbert Y; Kennedy, James L.; Müller, Daniel J.

In: Journal of Neural Transmission, Vol. 126, No. 1, 21.01.2019, p. 27-33.

Research output: Contribution to journalArticle

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AU - Maciukiewicz, Malgorzata

AU - Gorbovskaya, Ilona

AU - Tiwari, Arun K.

AU - Zai, Clement C.

AU - Freeman, Natalie

AU - Meltzer, Herbert Y

AU - Kennedy, James L.

AU - Müller, Daniel J.

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