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. Voineskos; Steven G. Potkin; Jeffrey A. Lieberman; Herbert Y. Meltzer; Gary Remington; James L. Kennedy

doi:10.3389/fphar.2018.00974

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

Psychiatry and Behavioral Sciences

Research output: Contribution to journal › Article › peer-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we conducted a meta-analysis specific to the relationship of HSPG2 rs2445142 with TD occurrence, while also adding our unpublished genotype data.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 language	English (US)
Article number	974
Journal	Frontiers in Pharmacology
Volume	9
Issue number	SEP
DOIs	https://doi.org/10.3389/fphar.2018.00974
State	Published - 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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Zai, C. C., Lee, F. H., Tiwari, A. K., Lu, J. Y., De Luca, V., Maes, M. S., Herbert, D., Shahmirian, A., Cheema, S. Y., Zai, G. C., Atukuri, A., Sherman, M., Shaikh, S. A., Tampakeras, M., Freeman, N., King, N., Müller, D. J., Greenbaum, L., Lerer, B., ... Kennedy, J. L. (2018). Investigation of the HSPG2Gene in tardive dyskinesia-new data and meta-analysis. Frontiers in Pharmacology, 9(SEP), Article 974. https://doi.org/10.3389/fphar.2018.00974

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title = "Investigation of the HSPG2Gene in tardive dyskinesia-new data and meta-analysis",

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.",

keywords = "Meta-analysis, Perlecan/heparan sulfate proteoglycan 2 (HSPG2), Pharmacogenetics, Schizophrenia, Tardive dyskinesia",

author = "Zai, {Clement C.} and Lee, {Frankie H.} and Tiwari, {Arun K.} and Lu, {Justin Y.} and {De Luca}, Vincenzo and Maes, {Miriam S.} and Deanna Herbert and Anashe Shahmirian and Cheema, {Sheraz Y.} and Zai, {Gwyneth C.} and Anupama Atukuri and Michael Sherman and Shaikh, {Sajid A.} and Maria Tampakeras and Natalie Freeman and Nicole King and M{\"u}ller, {Daniel J.} and Lior Greenbaum and Bernard Lerer and Voineskos, {Aristotle N.} and Potkin, {Steven G.} and Lieberman, {Jeffrey A.} and Meltzer, {Herbert Y.} and Gary Remington and Kennedy, {James L.}",

year = "2018",

month = sep,

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doi = "10.3389/fphar.2018.00974",

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Zai, CC, Lee, FH, Tiwari, AK, Lu, JY, De Luca, V, Maes, MS, Herbert, D, Shahmirian, A, Cheema, SY, Zai, GC, Atukuri, A, Sherman, M, Shaikh, SA, Tampakeras, M, Freeman, N, King, N, Müller, DJ, Greenbaum, L, Lerer, B, Voineskos, AN, Potkin, SG, Lieberman, JA, Meltzer, HY, Remington, G & Kennedy, JL 2018, 'Investigation of the HSPG2Gene in tardive dyskinesia-new data and meta-analysis', Frontiers in Pharmacology, vol. 9, no. SEP, 974. https://doi.org/10.3389/fphar.2018.00974

TY - JOUR

T1 - Investigation of the HSPG2Gene in tardive dyskinesia-new data and meta-analysis

AU - Zai, Clement C.

AU - Lee, Frankie H.

AU - Tiwari, Arun K.

AU - Lu, Justin Y.

AU - De Luca, Vincenzo

AU - Maes, Miriam S.

AU - Herbert, Deanna

AU - Shahmirian, Anashe

AU - Cheema, Sheraz Y.

AU - Zai, Gwyneth C.

AU - Atukuri, Anupama

AU - Sherman, Michael

AU - Shaikh, Sajid A.

AU - Tampakeras, Maria

AU - Freeman, Natalie

AU - King, Nicole

AU - Müller, Daniel J.

AU - Greenbaum, Lior

AU - Lerer, Bernard

AU - Voineskos, Aristotle N.

AU - Potkin, Steven G.

AU - Lieberman, Jeffrey A.

AU - Meltzer, Herbert Y.

AU - Remington, Gary

AU - Kennedy, James L.

PY - 2018/9/18

Y1 - 2018/9/18

N2 - 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.

AB - 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.

KW - Meta-analysis

KW - Perlecan/heparan sulfate proteoglycan 2 (HSPG2)

KW - Pharmacogenetics

KW - Schizophrenia

KW - Tardive dyskinesia

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DO - 10.3389/fphar.2018.00974

M3 - Article

C2 - 30283332

AN - SCOPUS:85055250183

SN - 1663-9812

VL - 9

JO - Frontiers in Pharmacology

JF - Frontiers in Pharmacology

IS - SEP

M1 - 974

ER -

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

Abstract

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Keywords

ASJC Scopus subject areas

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