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VRK2 gene expression in schizophrenia, bipolar disorder and healthy controls

  • Martin Tesli (a1), Katrine Verena Wirgenes (a1), Timothy Hughes (a2), Francesco Bettella (a1), Lavinia Athanasiu (a2), Eva S. Hoseth (a1), Mari Nerhus (a1), Trine V. Lagerberg (a1), Nils E. Steen (a3), Ingrid Agartz (a4), Ingrid Melle (a5), Ingrid Dieset (a5), Srdjan Djurovic (a6) and Ole A. Andreassen (a1)...
Abstract
Background

Common variants in the Vaccinia-related kinase 2 (VRK2) gene have been associated with schizophrenia, but the relevance of its encoded protein VRK2 in the disorder remains unclear.

Aims

To identify potential differences in VRK2 gene expression levels between schizophrenia, bipolar disorder, psychosis not otherwise specified (PNOS) and healthy controls.

Method

VRK2 mRNA level was measured in whole blood in 652 individuals (schizophrenia, n = 201; bipolar disorder, n = 167; PNOS, n = 61; healthy controls, n = 223), and compared across diagnostic categories and subcategories. Additionally, we analysed for association between 1566 VRK2 single nucleotide polymorphisms and mRNA levels.

Results

We found lower VRK2 mRNA levels in schizophrenia compared with healthy controls (P<10–12), bipolar disorder (P<10–12) and PNOS (P = 0.0011), and lower levels in PNOS than in healthy controls (P = 0.0042) and bipolar disorder (P = 0.00026). Expression quantitative trait loci in close proximity to the transcription start site of the short isoforms of the VRK2 gene were identified.

Conclusions

Altered VRK2 gene expression seems specific for schizophrenia and PNOS, which is in accordance with findings from genome-wide association studies. These results suggest that reduced VRK2 mRNA levels are involved in the underlying mechanisms in schizophrenia spectrum disorders.

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Copyright
Corresponding author
Ole A. Andreassen, MD, PhD, NORMENT, KG Jebsen Centre for Psychosis Research, Building 49, Oslo University Hospital, Ullevål, Kirkeveien 166, PO Box 4956 Nydalen, 0424 Oslo, Norway. Email: m.s.tesli@medisin.uio.no
Footnotes
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These authors contributed equally to this work.

Declaration of interest

M.T. received speaker's honorarium from Medivir. O.A.A. received speaker's honoraria from GlaxoSmithKline, Lundbeck and Otsuka.

Footnotes
References
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VRK2 gene expression in schizophrenia, bipolar disorder and healthy controls

  • Martin Tesli (a1), Katrine Verena Wirgenes (a1), Timothy Hughes (a2), Francesco Bettella (a1), Lavinia Athanasiu (a2), Eva S. Hoseth (a1), Mari Nerhus (a1), Trine V. Lagerberg (a1), Nils E. Steen (a3), Ingrid Agartz (a4), Ingrid Melle (a5), Ingrid Dieset (a5), Srdjan Djurovic (a6) and Ole A. Andreassen (a1)...
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