Genetic schizophrenia risk variants jointly modulate total brain and white matter volume

Terwisscha van Scheltinga, Afke F., Bakker, Steven C., van Haren, Neeltje E. M., Derks, Eske M., Buizer-Voskamp, Jacobine E., Boos, Heleen B. M., Cahn, Wiepke, Pol, Hilleke E. Hulshoff, Ripke, Stephan, Ophoff, Roel A., Kahn, Rene S., Psychiatric Genome-wide Association Study Consortium, Mowry, Bryan J., McGrath, John J ., Nertney, Deborah A ., Brown, Matthew A., Danoy, Patrick A. and Catts, Stanley V. (2013) Genetic schizophrenia risk variants jointly modulate total brain and white matter volume. Biological Psychiatry, 73 6: 525-531. doi:10.1016/j.biopsych.2012.08.017

Author Terwisscha van Scheltinga, Afke F.
Bakker, Steven C.
van Haren, Neeltje E. M.
Derks, Eske M.
Buizer-Voskamp, Jacobine E.
Boos, Heleen B. M.
Cahn, Wiepke
Pol, Hilleke E. Hulshoff
Ripke, Stephan
Ophoff, Roel A.
Kahn, Rene S.
Psychiatric Genome-wide Association Study Consortium
Mowry, Bryan J.
McGrath, John J .
Nertney, Deborah A .
Brown, Matthew A.
Danoy, Patrick A.
Catts, Stanley V.
Title Genetic schizophrenia risk variants jointly modulate total brain and white matter volume
Journal name Biological Psychiatry   Check publisher's open access policy
ISSN 0006-3223
Publication date 2013-03-15
Sub-type Article (original research)
DOI 10.1016/j.biopsych.2012.08.017
Volume 73
Issue 6
Start page 525
End page 531
Total pages 7
Place of publication Philadelphia, United States
Publisher Elsevier
Language eng
Formatted abstract
Background: Thousands of common single nucleotide polymorphisms (SNPs) are weakly associated with schizophrenia. It is likely that subsets of disease-associated SNPs are associated with distinct heritable disease-associated phenotypes. Therefore, we examined the shared genetic susceptibility modulating schizophrenia and brain volume.

Methods: Odds ratios for genome-wide SNP data were calculated in the sample collected by the Psychiatric Genome-wide Association Study Consortium (8690 schizophrenia patients and 11,831 control subjects, excluding subjects from the present study). These were used to calculate individual polygenic schizophrenia (risk) scores in an independent sample of 152 schizophrenia patients and 142 healthy control subjects with available structural magnetic resonance imaging scans.

Results: In the entire group, the polygenic schizophrenia score was significantly associated with total brain volume (R2=.048, p=1.6×10−4) and white matter volume (R2=.051, p=8.6×10−5) equally in patients and control subjects. The number of (independent) SNPs that substantially influenced both disease risk and white matter (n=2020) was much smaller than the entire set of SNPs that modulated disease status (n=14,751). From the set of 2020 SNPs, a group of 186 SNPs showed most evidence for association with white matter volume and an explorative functional analysis showed that these SNPs were located in genes with neuronal functions.

Conclusions: These results indicate that a relatively small subset of schizophrenia genetic risk variants is related to the (normal) development of white matter. This, in turn, suggests that disruptions in white matter growth increase the susceptibility to develop schizophrenia.
Keyword Endophenotype
Structural MRI
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2014 Collection
School of Medicine Publications
UQ Diamantina Institute Publications
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