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The effect of a genetic variant at the schizophrenia associated AS3MT/BORCS7 locus on striatal dopamine function: A PET imaging study

D'Ambrosio, Enrico, Dahoun, Tarik, Pardinas, Antonio F., Veronese, Mattia, Bloomfield, Michael A.P., Jauhar, Sameer, Bonoldi, Ilaria, Rogdaki, Maria, Froudist-Walsh, Sean, Walters, James T. R. and Howes, Oliver D. 2019. The effect of a genetic variant at the schizophrenia associated AS3MT/BORCS7 locus on striatal dopamine function: A PET imaging study. Psychiatry Research: Neuroimaging 291 , pp. 34-41. 10.1016/j.pscychresns.2019.07.005
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Abstract

One of the most statistically significant loci to result from large-scale GWAS of schizophrenia is 10q24.32. However, it is still unclear how this locus is involved in the pathoaetiology of schizophrenia. The hypothesis that presynaptic dopamine dysfunction underlies schizophrenia is one of the leading theories of the pathophysiology of the disorder. Supporting this, molecular imaging studies show evidence for elevated dopamine synthesis and release capacity. Thus, altered dopamine function could be a potential mechanism by which this genetic variant acts to increase the risk of schizophrenia. We therefore tested the hypothesis that the 10q24.32 region confers genetic risk for schizophrenia through an effect on striatal dopamine function. To this aim we investigated the in vivo relationship between a GWAS schizophrenia-associated SNP within this locus and dopamine synthesis capacity measured using [18F]-DOPA PET in healthy controls. 92 healthy volunteers underwent [18F]-DOPA PET scans to measure striatal dopamine synthesis capacity (indexed as Kicer) and were genotyped for the SNP rs7085104. We found a significant association between rs7085104 genotype and striatal Kicer. Our findings indicate that the mechanism mediating the 10q24.32 risk locus for schizophrenia could involve altered dopaminergic function. Future studies are needed to clarify the neurobiological pathway implicated in this association.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Publisher: Elsevier
ISSN: 0925-4927
Date of First Compliant Deposit: 20 August 2019
Date of Acceptance: 18 July 2019
Last Modified: 18 Oct 2019 06:38
URI: http://orca-mwe.cf.ac.uk/id/eprint/125021

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