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Variation in DISC1 is associated with anxiety, depression and emotional stability in elderly women

Molecular Psychiatry volume 15, pages 232–234 (2010)Cite this article

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A recent association study identified three single nucleotide polymorphisms (SNPs) (rs1538979, rs821577 and rs821633) in Disrupted in Schizophrenia 1 (DISC1) gene that, either independently or in combination, influence risk of schizophrenia and bipolar disorder.1 We investigated the association between these SNPs and the personality trait emotional stability/neuroticism (a potential endophenotype for mental illness), and anxiety and depression in two relatively healthy older Scottish cohorts (Lothian Birth Cohort of 1921 (LBC1921),2 n=360; and Lothian Birth Cohort of 1936 (LBC1936),3 n=1065).

Personality was assessed at a mean age of ∼81 years (LBC1921) or ∼70 years (LBC1936). Emotional stability was measured using the IPIP Big-Five 50-item inventory4 and, for LBC1936 only, neuroticism was assessed using the NEO five-factor inventory.5 Mood was assessed at a mean age of ∼79 years (LBC1921) or ∼70 years (LBC1936) using scores on the Hospital Anxiety and Depression scale (HADS).6 LBC1921 was genotyped on a Sequenom platform (Sequenom, San Diego, CA, USA)1 and LBC1936 using TaqMan (Applied Biosystems, Pleasonton, CA, USA) at the Wellcome Trust Clinical Research Facility, Edinburgh. Genotype frequencies did not differ significantly from the Hardy–Weinberg equilibrium (P>0.01) and were LBC1921 (LBC1936); rs1538979, C/C=262 (749); T/C=80 (230); T/T=10 (29), rs821577, G/G=61 (193); G/T=163 (492); T/T=118 (351) and rs821633, C/C=35 (94); C/T=128 (429); T/T=175 (483). Phenotypic outliers with z-scores greater than ±3 were removed before analyses. Descriptive statistics of the phenotypic variables are listed in the Supplementary Table. General linear modelling was performed in SPSS v13 (SPSSinc, Chicago, IL, USA) using carrier status (as defined in Hennah et al. (2008)1) for each SNP or combination of SNPs and sex as fixed factors. As previous studies have shown that variance in DISC1 has stronger effects in females than in males,1 the models were also run analysing males and females separately. LBC1921 and LBC1936 were first analysed separately and then, for HADS and emotional stability, combined analyses were performed with cohort added to the models as a fixed factor.

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Authors and Affiliations

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

    S E Harris, W Hennah, P A Thomson & D J Porteous

  2. Department of Psychology, Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK

    S E Harris, M Luciano & I J Deary

  3. Institute for Molecular Medicine Finland FIMM, Nordic EMBL Partnership for Molecular Medicine, Helsinki, Finland

    W Hennah

  4. Unit of Public Health Genomics, National Institute for Health and Welfare, Helsinki, Finland

    W Hennah

  5. Geriatric Medicine Unit, Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Royal Victoria, Edinburgh, UK

    J M Starr

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  1. S E Harris
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  2. W Hennah
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  3. P A Thomson
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  4. M Luciano
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  5. J M Starr
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  6. D J Porteous
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  7. I J Deary
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Correspondence to S E Harris.

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Supplementary Information accompanies the paper on the Molecular Psychiatry website (http://www.nature.com/mp)

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Harris, S., Hennah, W., Thomson, P. et al. Variation in DISC1 is associated with anxiety, depression and emotional stability in elderly women. Mol Psychiatry 15, 232–234 (2010). https://doi.org/10.1038/mp.2009.88

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