title: Predicting brain structure in population-based samples with biologically informed genetic scores for schizophrenia.
abstract: Schizophrenia is associated with brain structural abnormalities including gray and white matter volume reductions. Whether these alterations are caused by genetic risk variants for schizophrenia is unclear. Previous attempts to detect associations between polygenic factors for schizophrenia and structural brain phenotypes in healthy subjects have been negative or remain non-replicated. In this study, we used genetic risk scores that were based on the accumulated effect of selected risk variants for schizophrenia belonging to specific biological systems like synaptic function, neurodevelopment, calcium signaling, and glutamatergic neurotransmission. We hypothesized that this "biologically informed" approach would provide the missing link between genetic risk for schizophrenia and brain structural phenotypes. We applied whole-brain voxel-based morphometry (VBM) analyses in two population-based target samples and subsequent regions of interest (ROIs) analyses in an independent replication sample (total N = 2725). No consistent association between the genetic scores and brain volumes were observed in the investigated samples. These results suggest that in healthy subjects with a higher genetic risk for schizophrenia additional factors apart from common genetic variants (e.g., infection, trauma, rare genetic variants, or gene-gene interactions) are required to induce structural abnormalities of the brain. Further studies are recommended to test for possible gene-gene or gene-environment effects. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.|German Center for Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Van der Auwera
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Wittfeld
authors.affiliation: Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.|Centre for Cognitive Neuroimaging, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.
authors.forename: Elena
authors.initials: E
authors.lastname: Shumskaya
authors.affiliation: Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Janita
authors.initials: J
authors.lastname: Bralten
authors.affiliation: Centre for Cognitive Neuroimaging, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.
authors.forename: Marcel P
authors.initials: MP
authors.lastname: Zwiers
authors.affiliation: Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: A Marten H
authors.initials: AM
authors.lastname: Onnink
authors.affiliation: Centre for Cognitive Neuroimaging, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.
authors.forename: Niccolo
authors.initials: N
authors.lastname: Usberti
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.|German Center for Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Hertel
authors.affiliation: Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.|DZHK-German Centre for Cardiovascular Research, Partner Site Greifswald, Greifswald, Germany.|DZD-German Centre for Diabetes Research, Greifswald, Germany.
authors.forename: Henry
authors.initials: H
authors.lastname: Völzke
authors.affiliation: Interfaculty Institute for Genetics and, Functional Genomics, University of Greifswald, Greifswald, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Völker
authors.affiliation: Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Hosten
authors.affiliation: Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.|Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Barbara
authors.initials: B
authors.lastname: Franke
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.|German Center for Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, Germany.
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Grabe
mesh_terms: D000328:Adult; D001921:Brain / Q000033:anatomy & histology / Q000503:physiopathology*; D001931:Brain Mapping / Q000379:methods; D005260:Female; D005544:Forecasting; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D009929:Organ Size / Q000235:genetics; D012307:Risk Factors; D012559:Schizophrenia / Q000235:genetics* / Q000503:physiopathology*
keywords: BIG study; SHIP study; biologically informed genetic score; schizophrenia; voxel-based morphometry