Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter to the Editor
  • Published:

Association of white matter integrity with genetic variation in an exonic DISC1 SNP

Molecular Psychiatry volume 16, pages 688–689 (2011)Cite this article

Subjects

The Disrupted-in-Schizophrenia-1 (DISC1) gene was first identified at the breakpoint of a translocation between chromosomes 1 and 11 that co-segregated with a broad psychiatric phenotype in a large Scottish family,1, 2 and subsequent association studies have shown that common genetic variants in DISC1 convey susceptibility to schizophrenia, bipolar disorder and other psychiatric disorders.3 DISC1 is involved in several neurodevelopmental processes, including the development of white matter,4, 5, 6 and white matter abnormalities are well-established in schizophrenia and bipolar disorder7 and have a high genetic correlation with susceptibility to both disorders.8, 9 Here, we report an association between a common missense variant in DISC1, rs821616 (Ser704Cys), previously associated with schizophrenia,3 and white matter integrity as measured by diffusion tensor-magnetic resonance imaging.

DNA samples and diffusion tensor-magnetic resonance imaging scans were obtained from 87 healthy individuals between the age of 16 and 25 years. Participants were excluded for major medical or neurological disorders, head injury or learning disability, as well as for personal or family history of psychiatric disorders and history of harmful substance abuse. Genotypes were determined using TaqMan polymerase chain reaction (PCR, TaqMan, AssayByDesign, Applied Biosystems, Foster City, CA, USA). The number of subjects in each genotype group did not significantly deviate from the Hardy–Weinberg equilibrium (TT homozygotes: N=10, TA heterozygotes: N=38, AA homozygotes: N=39, P>0.99). The genotype groups did not significantly differ with respect to age, sex, intelligence quotient (Wechsler Abbreviated Scale of Intelligence), parental occupation or history of substance abuse (see Supplementary Table 1).

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

References

  1. Blackwood DHR, Fordyce A, Walker St MT, Clair DM, Porteous DJ, Muir WJ . Am J Hum Genet 2001; 69: 428–433.

    Article  CAS  Google Scholar 

  2. Millar JK, Wilson-Annan JC, Anderson S, Christie S, Taylor MS, Semple CA et al. Hum Mol Genet 2000; 9: 1415–1423.

    Article  CAS  Google Scholar 

  3. Callicott JH, Straub RE, Pezawas L, Egan MF, Mattay VS, Hariri AR et al. Proc Natl Acad Sci USA 2005; 102: 8627–8632.

    Article  CAS  Google Scholar 

  4. Mao Y, Ge X, Frank CL, Madison JM, Koehler AN, Doud MK et al. Cell 2009; 136: 1017–1031.

    Article  CAS  Google Scholar 

  5. Brandon NJ, Millar JK, Korth C, Sive H, Singh KK, Sawa A . J Neurosci 2009; 29: 12768–12775.

    Article  CAS  Google Scholar 

  6. Wood JD, Bonath F, Kumar S, Ross CA, Cunliffe VT . Hum Mol Genet 2009; 18: 391–404.

    Article  CAS  Google Scholar 

  7. Sussmann JE, Lymer GKS, McKirdy J, Moorhead TWJ, Muñoz-Maniega S, Job D et al. Bipolar Disord 2009; 11: 11–18.

    Article  Google Scholar 

  8. van der Schot AC, Vonk R, Brans RGH, van Haren NEM, Koolschijn PCMP, Nuboer V et al. Arch Gen Psychiatry 2009; 66: 142–151.

    Article  Google Scholar 

  9. Hulshoff Pol HE, Schnak HG, Mandl RCW, Brans RGH, van Haren NEM, Baaré WFC et al. Neuroimage 2006; 31: 482–488.

    Article  Google Scholar 

  10. Smith SM, Jenkinson M, Johansen-Berg H, Rueckert D, Nickols TE, Mackay CE et al. Neuroimage 2006; 31: 1487–1505.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK

    E Sprooten, J E Sussmann, T W Moorhead, H C Whalley, J Hall, S M Lawrie & A M McIntosh

  2. MRC Centre for Regenerative Medicine, Royal Infirmary, Edinburgh, UK

    C ffrench-Constant

  3. Departments of Psychiatry and Diagnostic Radiology, Yale School of Medicine, New Haven, CT, USA

    H P Blumberg

  4. Department of Clinical Neurosciences, Centre for Clinical Brain Sciences, University of Edinburgh, Western General Hospital, Edinburgh, UK

    M E Bastin

  5. Medical and Radiological Sciences (Medical Physics), University of Edinburgh, Western General Hospital, Edinburgh, UK

    M E Bastin

Authors
  1. E Sprooten
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J E Sussmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T W Moorhead
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H C Whalley
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. C ffrench-Constant
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. H P Blumberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M E Bastin
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. J Hall
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. S M Lawrie
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. A M McIntosh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to E Sprooten.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies the paper on the Molecular Psychiatry website

Supplementary information

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sprooten, E., Sussmann, J., Moorhead, T. et al. Association of white matter integrity with genetic variation in an exonic DISC1 SNP. Mol Psychiatry 16, 688–689 (2011). https://doi.org/10.1038/mp.2011.15

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/mp.2011.15

This article is cited by

Search

Advanced search

Quick links