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HapMap tag-SNP analysis confirms a role for COMT in schizophrenia risk and reveals a novel association

Published online by Cambridge University Press:  15 April 2020

J. Voisey ,
C.D. Swagell ,
I.P. Hughes ,
B.R. Lawford ,
R.M. Young  and
C.P. Morris
J. Voisey
Affiliation:
Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia
C.D. Swagell
Affiliation:
Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia
I.P. Hughes
Affiliation:
Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia
B.R. Lawford
Affiliation:
Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia Division of Mental Health, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia
R.M. Young
Affiliation:
Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia
C.P. Morris*
Affiliation:
Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia
*
*Corresponding author. Tel.: +61 7 31386196; fax: +61 7 31386030. E-mail address: p.morris@qut.edu.au
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Abstract

Catechol-O-methyl transferase (COMT) encodes an enzyme involved in the metabolism of dopamine and maps to a commonly deleted region that increases schizophrenia risk. A non-synonymous polymorphism (rs4680) in COMT has been previously found to be associated with schizophrenia and results in altered activity levels of COMT. Using a haplotype block-based gene-tagging approach we conducted an association study of seven COMT single nucleotide polymorphisms (SNPs) in 160 patients with a DSM-IV diagnosis of schizophrenia and 250 controls in an Australian population. Two polymorphisms including rs4680 and rs165774 were found to be significantly associated with schizophrenia. The rs4680 results in a Val/Met substitution but the strongest association was shown by the novel SNP, rs165774, which may still be functional even though it is located in intron five. Individuals with schizophrenia were more than twice as likely to carry the GG genotype compared to the AA genotype for both the rs165774 and rs4680 SNPs. This association was slightly improved when males were analysed separately possibly indicating a degree of sexual dimorphism. Our results confirm that COMT is a good candidate for schizophrenia risk, by replicating the association with rs4680 and identifying a novel SNP association.

Keywords

COMTSchizophreniaGenotypingPolymorphismSexual dimorphism
Type
Original articles
Information
European Psychiatry , Volume 27 , Issue 5 , July 2012 , pp. 372 - 376
Copyright
Copyright © Elsevier Masson SAS 2012

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