title: Genetic influences on schizophrenia and subcortical brain volumes: large-scale proof of concept.
abstract: Schizophrenia is a devastating psychiatric illness with high heritability. Brain structure and function differ, on average, between people with schizophrenia and healthy individuals. As common genetic associations are emerging for both schizophrenia and brain imaging phenotypes, we can now use genome-wide data to investigate genetic overlap. Here we integrated results from common variant studies of schizophrenia (33,636 cases, 43,008 controls) and volumes of several (mainly subcortical) brain structures (11,840 subjects). We did not find evidence of genetic overlap between schizophrenia risk and subcortical volume measures either at the level of common variant genetic architecture or for single genetic markers. These results provide a proof of concept (albeit based on a limited set of structural brain measures) and define a roadmap for future studies investigating the genetic covariance between structural or functional brain phenotypes and risk for psychiatric disorders.
authors: Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.|Department of Psychiatry, Radboud University Medical Center, Nijmegen, The Netherlands.|Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.
authors: Barbara
authors: B
authors: Franke
authors: Imaging Genetics Center, Mark and Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of the University of Southern California, Marina del Rey, CA, USA.|Neurogenetics Program, Department of Neurology, UCLA School of Medicine, Los Angeles, USA.
authors: Jason L
authors: JL
authors: Stein
authors: Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.|Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.|Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, CCM, Berlin, Germany.
authors: Stephan
authors: S
authors: Ripke
authors: Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.|Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
authors: Verneri
authors: V
authors: Anttila
authors: Imaging Genetics Center, Mark and Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of the University of Southern California, Marina del Rey, CA, USA.
authors: Derrek P
authors: DP
authors: Hibar
authors: Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.|Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.
authors: Kimm J E
authors: KJE
authors: van Hulzen
authors: Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.|Department of Psychiatry, Radboud University Medical Center, Nijmegen, The Netherlands.|Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.|Department of Cognitive Neuroscience, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Alejandro
authors: A
authors: Arias-Vasquez
authors: Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.|Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.|Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
authors: Jordan W
authors: JW
authors: Smoller
authors: FMRIB Centre, University of Oxford, United Kingdom.|Department of Statistics & WMG, University of Warwick, Coventry, United Kingdom.
authors: Thomas E
authors: TE
authors: Nichols
authors: Departments of Psychiatry & Human Genetics, Virginia Commonwealth University, Richmond, VA, USA.
authors: Michael C
authors: MC
authors: Neale
authors: Division of Psychiatry, Royal Edinburgh Hospital, Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, United Kingdom.
authors: Andrew M
authors: AM
authors: McIntosh
authors: Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.|Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.|Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
authors: Phil
authors: P
authors: Lee
authors: Intramural Research Program, National Institutes of Health, US Dept of Health & Human Services, Bethesda, USA.
authors: Francis J
authors: FJ
authors: McMahon
authors: Central Institute of Mental Health, Medical Faculty Mannheim, University Heidelberg, Mannheim, Germany.
authors: Andreas
authors: A
authors: Meyer-Lindenberg
authors: Department of Biomedicine, Aarhus University, Aarhus, Denmark.|The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus and Copenhagen, Denmark.|Center for integrated Sequencing, iSEQ, Aarhus University, Aarhus, Denmark.
authors: Manuel
authors: M
authors: Mattheisen
authors: NORMENT - KG Jebsen Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
authors: Ole A
authors: OA
authors: Andreassen
authors: Center for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry and Psychotherapy, University Medical Center, Goettingen, Germany.
authors: Oliver
authors: O
authors: Gruber
authors: Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales (UNSW), Sydney, Australia.|Neuropsychiatric Institute, Prince of Wales Hospital, Sydney, Australia.
authors: Perminder S
authors: PS
authors: Sachdev
authors: Department of Psychiatry, University Hospital Marqués de Valdecilla, School of Medicine, University of Cantabria-IDIVAL, Santander, Spain.|Cibersam (Centro Investigación Biomédica en Red Salud Mental), Madrid, Spain.
authors: Roberto
authors: R
authors: Roiz-Santiañez
authors: Center for Neuroimaging, Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, USA.|Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, USA.|Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, USA.
authors: Andrew J
authors: AJ
authors: Saykin
authors: Department of Child and Adolescent Psychiatry, Faculty of Medicine and University Hospital, TU Dresden, Dresden, Germany.
authors: Stefan
authors: S
authors: Ehrlich
authors: Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales (UNSW), Sydney, Australia.
authors: Karen A
authors: KA
authors: Mather
authors: Georgia State University, Atlanta, USA.|Mind Research Network, Albuquerque, NM, USA.
authors: Jessica A
authors: JA
authors: Turner
authors: Central Institute of Mental Health, Medical Faculty Mannheim, University Heidelberg, Mannheim, Germany.
authors: Emanuel
authors: E
authors: Schwarz
authors: Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales (UNSW), Sydney, Australia.
authors: Anbupalam
authors: A
authors: Thalamuthu
authors: Intramural Research Program, National Institutes of Health, US Dept of Health & Human Services, Bethesda, USA.
authors: Yin Yao
authors: YY
authors: Shugart
authors: QIMR Berghofer Medical Research Institute, Brisbane, Australia.
authors: Yvonne Yw
authors: YY
authors: Ho
authors: QIMR Berghofer Medical Research Institute, Brisbane, Australia.
authors: Nicholas G
authors: NG
authors: Martin
authors: QIMR Berghofer Medical Research Institute, Brisbane, Australia.|School of Psychology, University of Queensland, Brisbane, Australia.
authors: Margaret J
authors: MJ
authors: Wright
authors: MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK.|National Centre for Mental Health, Cardiff University, Cardiff, UK.
authors: Michael C
authors: MC
authors: O'Donovan
authors: Imaging Genetics Center, Mark and Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of the University of Southern California, Marina del Rey, CA, USA.
authors: Paul M
authors: PM
authors: Thompson
authors: Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.|Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.|Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.|Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
authors: Benjamin M
authors: BM
authors: Neale
authors: QIMR Berghofer Medical Research Institute, Brisbane, Australia.
authors: Sarah E
authors: SE
authors: Medland
authors: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.|Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.|Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA.
authors: Patrick F
authors: PF
authors: Sullivan
mesh_terms: D001921:Brain / Q000473:pathology*; D058068:Endophenotypes; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D015810:Linkage Disequilibrium; D008279:Magnetic Resonance Imaging; D059906:Neuroimaging; D009929:Organ Size; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology*