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Schizophrenia risk variants modulate white matter volume across the psychosis spectrum: Evidence from two independent cohorts

Oertel-Knöchel, Viola, Lancaster, Thomas ORCID:, Knöchel, Christian, Stäblein, Michael, Storchak, Helena, Reinke, Britta, Jurcoane, Alina, Kniep, Jonathan, Prvulovic, David, Mantripragada, Kiran Kumar ORCID:, Tansey, Katherine E., O'Donovan, Michael Conlon ORCID:, Owen, Michael John ORCID: and Linden, David Edmund Johannes ORCID: 2015. Schizophrenia risk variants modulate white matter volume across the psychosis spectrum: Evidence from two independent cohorts. NeuroImage: Clinical 7 , pp. 764-770. 10.1016/j.nicl.2015.03.005

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Polygenic risk scores, based on risk variants identified in genome-wide-association-studies (GWAS), explain a considerable portion of the heritability for schizophrenia (SZ) and bipolar disorder (BD). However, little is known about the combined effects of these variants, although polygenic neuroimaging has developed into a powerful tool of translational neuroscience. In this study, we used genome wide significant SZ risk variants to test the predictive capacity of the polygenic model and explored potential associations with white matter volume, a key candidate in imaging phenotype for psychotic disorders. By calculating the combined additive schizophrenia risk of seven SNPs (significant hits from a recent schizophrenia GWAS study), we show that increased additive genetic risk for SZ was associated with reduced white matter volume in a group of participants (n = 94) consisting of healthy individuals, SZ first-degree relatives, SZ patients and BD patients. This effect was also seen in a second independent sample of healthy individuals (n = 89). We suggest that a moderate portion of variance (~4%) of white matter volume can be explained by the seven hits from the recent schizophrenia GWAS. These results provide evidence for associations between cumulative genetic risk for schizophrenia and intermediate neuroimaging phenotypes in models of psychosis. Our work contributes to a growing body of literature suggesting that polygenic risk may help to explain white matter alterations associated with familial risk for psychosis.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Neuroscience and Mental Health Research Institute (NMHRI)
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Publisher: Elsevier
ISSN: 2213-1582
Funders: MRC
Date of First Compliant Deposit: 30 March 2016
Date of Acceptance: 8 March 2015
Last Modified: 26 May 2023 17:57

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