Investigation of the HSPG2Gene in tardive dyskinesia-new data and meta-analysis

Clement C. Zai*, Frankie H. Lee, Arun K. Tiwari, Justin Y. Lu, Vincenzo De Luca, Miriam S. Maes, Deanna Herbert, Anashe Shahmirian, Sheraz Y. Cheema, Gwyneth C. Zai, Anupama Atukuri, Michael Sherman, Sajid A. Shaikh, Maria Tampakeras, Natalie Freeman, Nicole King, Daniel J. Müller, Lior Greenbaum, Bernard Lerer, Aristotle N. VoineskosSteven G. Potkin, Jeffrey A. Lieberman, Herbert Y. Meltzer, Gary Remington, James L. Kennedy

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Tardive dyskinesia (TD) is a movement disorder that may occur after extended use of antipsychotic medications. The etiopathophysiology is unclear; however, genetic factors play an important role. The Perlecan (HSPG2) gene was found to be significantly associated with TD in Japanese schizophrenia patients, and this association was subsequently replicated by an independent research group. To add to the evidence for this gene in TD, we conducted a meta-analysis specific to the relationship of HSPG2 rs2445142 with TD occurrence, while also adding our unpublished genotype data. Overall, we found a significant association of the G allele with TD occurrence (p = 0.0001); however, much of the effect appeared to originate from the discovery dataset. Nonetheless, most study samples exhibit the same trend of association with TD for the G allele. Our findings encourage further genetic and molecular studies of HSPG2 in TD.

Original languageEnglish (US)
Article number974
JournalFrontiers in Pharmacology
Volume9
Issue numberSEP
DOIs
StatePublished - Sep 18 2018

Funding

CZ, AT, and JK are supported by the Genome Canada Genomic Applications Partnership Program (GAPP) and the CAMH Foundation. DM was supported by the Canadian Institutes of Health Research (CIHR Operating Grant MOP 142192), the National Institutes of Health (R01MH085801), the CAMH Foundation (Joanne Murphy Professorship) and received a Brain & Behaviour Research (NARSAD) Independent Investigator Award, the Michael Smith New Investigator Salary Prize for Research in Schizophrenia (CIHR) and an Early Researcher Award by the Ministry of Research and Innovation of Ontario. GR was supported by the Canadian Institutes of Health Research (CIHR), as well as the Research Hospital Fund – Canadian Foundation for Innovation (RHF-CFI). We thank the Ministry of Research and Innovation of Ontario, for funding the IMPACT project. We would also like to express gratitude toward Larry and Judy Tanenbaum for their generous support in creating the Tanenbaum Centre for Pharmacogenetics, which is advancing research for the CAMH Pharmacogenetic Program.

Keywords

  • Meta-analysis
  • Perlecan/heparan sulfate proteoglycan 2 (HSPG2)
  • Pharmacogenetics
  • Schizophrenia
  • Tardive dyskinesia

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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