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A 5′ promoter region SNP in NRG1 is associated with schizophrenia risk and type III isoform expression

Molecular Psychiatry volume 14, pages 741–743 (2009)Cite this article

NRG1 is a schizophrenia candidate gene which regulates brain development and neural function. The minor allele of rs7014762 in the NRG1 5′ core promoter was associated with schizophrenia (P=0.031), and it significantly predicted reduced NRG1 type III isoform expression in post-mortem human brain of schizophrenia cases (P=0.001). Our results provide additional evidence for transcriptional dysregulation as a biological mechanism implicating NRG1 in schizophrenia risk.

Association between NRG1 and schizophrenia was originally discovered through haplotype analysis in an Icelandic sample (HAPICE) at the 5′ end of the gene1 and further replicated in a Scottish population.2 In this report, we examined association between schizophrenia and the NRG1 single nucleotide polymorphism (SNP) rs7014762 because it is situated within a core promoter region3 and is physically proximal (87 bp) to a functional SNP, which has been shown to influence NRG1 type IV isoform expression.4 In addition to clinical association analyses, we validated the functional effects of rs7014762 by testing for effects on mRNA expression in post-mortem human brain.

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Authors and Affiliations

  1. Genes, Cognition and Psychosis Program, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA

    K K Nicodemus, A J Law, A Luna, R Vakkalanka, R E Straub, J E Kleinman & D R Weinberger

  2. Department of Statistical Genetics, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK

    K K Nicodemus

  3. Department of Clinical Pharmacology, Old Road Campus Research Building, University of Oxford, Headington, Oxford, UK

    K K Nicodemus

  4. Department of Psychiatry, Warneford Hospital, University of Oxford, Warneford Lane, Headington, Oxford, UK

    A J Law

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  1. K K Nicodemus
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  2. A J Law
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  3. A Luna
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  4. R Vakkalanka
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  5. R E Straub
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  6. J E Kleinman
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  7. D R Weinberger
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Correspondence to D R Weinberger.

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Nicodemus, K., Law, A., Luna, A. et al. A 5′ promoter region SNP in NRG1 is associated with schizophrenia risk and type III isoform expression. Mol Psychiatry 14, 741–743 (2009). https://doi.org/10.1038/mp.2008.150

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