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dc.contributor.authorTerwisscha van Scheltinga, Afke F
dc.contributor.authorBakker, Steven C
dc.contributor.authorvan Haren, Neeltje E M
dc.contributor.authorDerks, Eske M
dc.contributor.authorBuizer-Voskamp, Jacobine E
dc.contributor.authorBoos, Heleen B M
dc.contributor.authorCahn, Wiepke
dc.contributor.authorHulshoff Pol, Hilleke E
dc.contributor.authorRipke, Stephan
dc.contributor.authorOphoff, Roel A
dc.contributor.authorKahn, René S
dc.contributor.authorSigurdsson, Engilbert
dc.date.accessioned2014-05-22T14:03:51Z
dc.date.available2014-05-22T14:03:51Z
dc.date.issued2013-03-15
dc.date.submitted2014-05-22
dc.identifier.citationBiol. Psychiatry 2013, 73(6):525-31en
dc.identifier.issn1873-2402
dc.identifier.pmid23039932
dc.identifier.doi10.1016/j.biopsych.2012.08.017
dc.identifier.urihttp://hdl.handle.net/2336/317312
dc.descriptionTo access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.en
dc.description.abstractThousands 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.
dc.description.abstractOdds 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.
dc.description.abstractIn 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.
dc.description.abstractThese 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.
dc.description.sponsorshipZorg Onderzoek Nederland Medische Wetenschappen 91686137 Dutch Brain Foundation 14F06(2)-34 Top Institute Pharma T5-203 Medische Wetenschappen, within the Mental Health program 10.000.1001 National Institute of Mental Health RO1 MG078075 Psychiatric Genomics Consortium Eli Lilly Janssen Pharmaceutica GlaxoSmithKline Bristol-Myers Squibb AstraZeneca Pharmaceuticals Pfizer Forest Pharmaceuticals Novartis Solvay Generation Scotland Genetics Health Initiative Organon Foundation for the National Institutes of Health Shire Forest Merck PGxHealth (a division of Clinical Data, Inc.) Roche Diagnostics Vanda Pharmaceuticals Eli Lilly Company Golden Helix, Inc. InforMed Insights Janssen EGIS H. Lundbeck A/S Richter Schering-Plough Johnson Johnson Janssen-Cilag Hospira (Mayne) Hospira Janssen Cilag Denmark-Aarhus groupen
dc.language.isoenen
dc.publisherElsevier Scienceen
dc.relation.urlhttp://dx.doi.org/10.1016/j.biopsych.2012.08.017en
dc.relation.urlhttp://www.sciencedirect.com/science/article/pii/S0006322312007275#en
dc.rightsArchived with thanks to Biological psychiatryen
dc.subject.meshAdulten
dc.subject.meshAtrophyen
dc.subject.meshBrainen
dc.subject.meshCase-Control Studiesen
dc.subject.meshFemaleen
dc.subject.meshGenetic Predisposition to Diseaseen
dc.subject.meshGenome-Wide Association Studyen
dc.subject.meshGenotypeen
dc.subject.meshHumansen
dc.subject.meshMaleen
dc.subject.meshNerve Fibers, Myelinateden
dc.subject.meshPhenotypeen
dc.subject.meshPolymorphism, Single Nucleotideen
dc.subject.meshSchizophreniaen
dc.titleGenetic schizophrenia risk variants jointly modulate total brain and white matter volume.en
dc.typeArticleen
dc.contributor.departmentUniv Med Ctr Utrecht, Rudolf Magnus Inst Neurosci, Dept Psychiat, NL-3584 CX Utrecht, Netherlands Univ Amsterdam, Acad Med Ctr, Dept Psychiat, NL-1105 AZ Amsterdam, Netherlands Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA USA. Landspitali Univ Hospital Reykjavik Icelanden
dc.identifier.journalBiological psychiatryen
dc.rights.accessNational Consortium - Landsaðganguren
html.description.abstractThousands 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.
html.description.abstractOdds 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.
html.description.abstractIn 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.
html.description.abstractThese 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.


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