Analysis of schizophrenia-associated genetic markers in the HLA region as risk factors for tardive dyskinesia

Ruoyu Wang; Justin Y Lu; Deanna Herbert; Jeffrey A Lieberman; Herbert Y Meltzer; Arun K Tiwari; Gary Remington; James L Kennedy; Clement C Zai

doi:10.1002/hup.2898

Analysis of schizophrenia-associated genetic markers in the HLA region as risk factors for tardive dyskinesia

Hum Psychopharmacol. 2024 Apr 27:e2898. doi: 10.1002/hup.2898. Online ahead of print.

Authors

Ruoyu Wang¹, Justin Y Lu¹, Deanna Herbert¹, Jeffrey A Lieberman², Herbert Y Meltzer³, Arun K Tiwari^{1

4}, Gary Remington^{1

4

5}, James L Kennedy^{1

4

5}, Clement C Zai^{1

4

5

6

7}

Affiliations

¹ Tanenbaum Centre for Pharmacogenetics, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
² Columbia University, New York State Psychiatric Institute, New York City, New York, USA.
³ Psychiatry and Behavioral Sciences, Pharmacology and Physiology, Chemistry of Life Processes Institute, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
⁴ Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
⁵ Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
⁶ Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
⁷ Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.

PMID: 38676936
DOI: 10.1002/hup.2898

Abstract

Objectives: The pathology of Tardive Dyskinesia (TD) has yet to be fully understood, but there have been proposed hypotheses for the cause of this condition. Our team previously reported a possible association of TD with the Complement Component C4 gene in the HLA region. In this study, we explored the HLA region further by examining two previously identified schizophrenia-associated HLA-region single-nucleotide polymorphisms (SNPs), namely rs13194504 and rs210133.

Methods: The SNPs rs13194504 and rs210133 were tested for association with the occurrence and severity of TD in a sample of 172 schizophrenia patients who were recruited for four studies from three different clinical sites in Canada and USA.

Results: The rs13194504 AA genotype was associated with decreased severity for TD as measured by Abnormal Involuntary Movement Scale (AIMS) scores (p = 0.047) but not for TD occurrence. SNP rs210133 was not significantly associated with either TD occurrence or AIMS scores.

Conclusion: Our findings suggest that the rs13194504 AA genotype may play a role in TD severity, while SNP rs210133 may not have a major role in the risk or severity of TD.

Keywords: genetic markers; pharmacogenetics; schizophrenia; tardive dyskinesia.

Abstract

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