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Association of DISC1 variants with age of onset in a population-based sample of recurrent major depression

Molecular Psychiatry volume 18, pages 745–747 (2013)Cite this article

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The majority of studies investigating the association of DISC1 and mental illness have focussed on clinically ascertained samples (reviewed in Bradshaw et al.1). Here, we provide evidence from a population-based study, Generation Scotland–Scottish Family Health Study (GS:SFHS2), for association between single-nucleotide polymorphisms (SNPs) in DISC1 and recurrent major depression (RMD). In addition, two recent publications identified SNPs that tag cis-acting factors affecting expression of DISC1 (eQTLs, expression quantitative trait loci).3, 4 Here, we show that these eQTLs are associated with age of onset, indicating that DISC1 expression levels may be linked to phenotype severity.

DISC1 was first implicated in RMD in a Scottish family with a translocation, t(1:11) (q42.1;q14.3), that interrupts the DISC1 gene resulting in an approximately 50% reduction in DISC1 expression in lymphoblastoid cell lines derived from translocation carriers. Thirty-four percent of the translocation carriers were diagnosed with RMD, 24% received a diagnosis of schizophrenia or bipolar disorder, giving a significant logarithm of odds (LOD) score of 4.5 for RMD alone.5 Association between DISC1 and RMD was subsequently also reported in case–control cohorts.4, 6, 7

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Authors and Affiliations

  1. Department of Medical Genetics, Molecular Medicine Centre, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK

    P A Thomson, G Hamilton, K L Evans & D J Porteous

  2. Centre for Cognitive Ageing and Cognitive Epidemiology, Medical Genetics Section, University of Edinburgh, Edinburgh, UK

    P A Thomson, G Hamilton, K L Evans & D J Porteous

  3. Division of Psychiatry, University of Edinburgh, Kennedy Tower, Royal Edinburgh Hospital, Edinburgh, UK

    D J MacIntyre

  4. BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK

    A Dominiczak

  5. Medical Research Institute, University of Dundee, Dundee, UK

    B H Smith & A Morris

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  1. P A Thomson
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  2. D J MacIntyre
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  3. G Hamilton
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  4. A Dominiczak
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  7. K L Evans
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  8. D J Porteous
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Correspondence to P A Thomson.

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Thomson, P., MacIntyre, D., Hamilton, G. et al. Association of DISC1 variants with age of onset in a population-based sample of recurrent major depression. Mol Psychiatry 18, 745–747 (2013). https://doi.org/10.1038/mp.2012.117

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