Back
Full-text
Journal article

Genetic contributors to risk of schizophrenia in the presence of a 22q11.2 deletion.

  • Cleynen I Department of Human Genetics, KU Leuven, Leuven, Belgium.
  • Engchuan W The Centre for Applied Genomics (TCAG), The Hospital for Sick Children, Toronto, ON, Canada.
  • Hestand MS Department of Human Genetics, KU Leuven, Leuven, Belgium.
  • Heung T Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, ON, Canada.
  • Holleman AM Department of Epidemiology, Emory University, Atlanta, GA, USA.
  • Johnston HR Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.
  • Monfeuga T MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK.
  • McDonald-McGinn DM Department of Pediatrics, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA, USA.
  • Gur RE Department of Psychiatry and Lifespan Brain Institute, Penn Medicine-CHOP, University of Pennsylvania, Philadelphia, PA, USA.
  • Morrow BE Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA.
  • Swillen A Department of Human Genetics, KU Leuven, Leuven, Belgium.
  • Vorstman JAS Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Bearden CE Departments of Psychiatry and Biobehavioral Sciences and Psychology, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA.
  • Chow EWC Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, ON, Canada.
  • van den Bree M MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK.
  • Emanuel BS Division of Human Genetics and 22q and You Center, the Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Vermeesch JR Department of Human Genetics, KU Leuven, Leuven, Belgium.
  • Warren ST Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.
  • Owen MJ MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK.
  • Chopra P Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.
  • Cutler DJ Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.
  • Duncan R Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.
  • Kotlar AV Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.
  • Mulle JG Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.
  • Voss AJ Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.
  • Zwick ME Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.
  • Diacou A Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA.
  • Golden A Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA.
  • Guo T Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA.
  • Lin JR Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA.
  • Wang T Department of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.
  • Zhang Z Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA.
  • Zhao Y Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA.
  • Marshall C Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
  • Merico D The Centre for Applied Genomics (TCAG), The Hospital for Sick Children, Toronto, ON, Canada.
  • Jin A Division of Human Genetics and 22q and You Center, the Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Lilley B Division of Human Genetics and 22q and You Center, the Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Salmons HI Division of Human Genetics and 22q and You Center, the Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Tran O Division of Human Genetics and 22q and You Center, the Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Holmans P MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK.
  • Pardinas A MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK.
  • Walters JTR MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK.
  • Demaerel W Department of Human Genetics, KU Leuven, Leuven, Belgium.
  • Boot E Dalglish Family 22q Clinic, Toronto General Hospital, University Health Network, Toronto, ON, Canada.
  • Butcher NJ Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, ON, Canada.
  • Costain GA Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, ON, Canada.
  • Lowther C Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, ON, Canada.
  • Evers R School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands.
  • van Amelsvoort TAMJ School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands.
  • van Duin E School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands.
  • Vingerhoets C School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands.
  • Breckpot J Department of Human Genetics, KU Leuven, Leuven, Belgium.
  • Devriendt K Department of Human Genetics, KU Leuven, Leuven, Belgium.
  • Vergaelen E Center for Human Genetics, University Hospitals Leuven, Leuven, Belgium.
  • Vogels A Department of Human Genetics, KU Leuven, Leuven, Belgium.
  • Crowley TB Division of Human Genetics and 22q and You Center, the Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • McGinn DE Division of Human Genetics and 22q and You Center, the Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Moss EM Division of Human Genetics and 22q and You Center, the Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Sharkus RJ Division of Human Genetics and 22q and You Center, the Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Unolt M Division of Human Genetics and 22q and You Center, the Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Zackai EH Department of Pediatrics, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA, USA.
  • Calkins ME Department of Psychiatry and Lifespan Brain Institute, Penn Medicine-CHOP, University of Pennsylvania, Philadelphia, PA, USA.
  • Gallagher RS Department of Psychiatry and Lifespan Brain Institute, Penn Medicine-CHOP, University of Pennsylvania, Philadelphia, PA, USA.
  • Gur RC Department of Psychiatry and Lifespan Brain Institute, Penn Medicine-CHOP, University of Pennsylvania, Philadelphia, PA, USA.
  • Tang SX Department of Psychiatry and Lifespan Brain Institute, Penn Medicine-CHOP, University of Pennsylvania, Philadelphia, PA, USA.
  • Fritsch R Universidad de Chile, Santiago, Chile.
  • Ornstein C Universidad de Chile, Santiago, Chile.
  • Repetto GM Clinica Alemana Universidad del Desarrollo, Santiago, Chile.
  • Breetvelt E Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
  • Duijff SN Department of Pediatrics, University Medical Center Utrecht, Utrecht, Netherlands.
  • Fiksinski A Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, ON, Canada.
  • Moss H MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK.
  • Niarchou M MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK.
  • Murphy KC Royal College of Surgeons in Ireland, Dublin, Ireland.
  • Prasad SE Royal College of Surgeons in Ireland, Dublin, Ireland.
  • Daly EM Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King's College London, London, UK.
  • Gudbrandsen M Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King's College London, London, UK.
  • Murphy CM Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King's College London, London, UK.
  • Murphy DG Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King's College London, London, UK.
  • Buzzanca A Department of Human Neurosciences, University Sapienza of Rome, Rome, Italy.
  • Fabio FD Department of Human Neurosciences, University Sapienza of Rome, Rome, Italy.
  • Digilio MC Ospedale Bambino Gesu Pediatric Hospital, Rome, Italy.
  • Pontillo M Child and Adolescence Neuropsychiatry Unit, Department of Neuroscience, IRCSS Bambino Gesù Children's Hospital of Rome, Rome, Italy.
  • Marino B Sapienza University, Rome, Italy.
  • Vicari S Child and Adolescence Neuropsychiatry Unit, Department of Neuroscience, IRCSS Bambino Gesù Children's Hospital of Rome, Rome, Italy.
  • Coleman K Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.
  • Cubells JF Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.
  • Ousley OY Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
  • Carmel M Felsenstein Medical Research Center, Petach Tikva, Israel.
  • Gothelf D Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
  • Mekori-Domachevsky E Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
  • Michaelovsky E Felsenstein Medical Research Center, Petach Tikva, Israel.
  • Weinberger R The Child Psychiatry Division, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Israel.
  • Weizman A Felsenstein Medical Research Center, Petach Tikva, Israel.
  • Kushan L Departments of Psychiatry and Biobehavioral Sciences and Psychology, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA.
  • Jalbrzikowski M Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Armando M Developmental Imaging and Psychopathology, Department of Psychiatry, University of Geneva, Geneva, Switzerland.
  • Eliez S Developmental Imaging and Psychopathology, Department of Psychiatry, University of Geneva, Geneva, Switzerland.
  • Sandini C Developmental Imaging and Psychopathology, Department of Psychiatry, University of Geneva, Geneva, Switzerland.
  • Schneider M Developmental Imaging and Psychopathology, Department of Psychiatry, University of Geneva, Geneva, Switzerland.
  • Béna FS Department of Medical Genetics, Geneva University Hospitals, Geneva, Switzerland.
  • Antshel KM Department of Psychology, Syracuse University, Syracuse, NY, USA.
  • Fremont W Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse, NY, USA.
  • Kates WR Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse, NY, USA.
  • Belzeaux R Pôle de psychiatrie, Hopital Sainte Marguerite, Batiment Solaris, APHM, Marseille, France.
  • Busa T Departement de Genetique Medicale Hôpital d'Enfants de la Timone, APHM, Marseille, France.
  • Philip N Departement de Genetique Medicale Aix Marseille Univ, INSERM, GMGF, APHM, Marseille, France.
  • Campbell LE University of Newcastle, Callaghan, Australia.
  • McCabe KL University of Newcastle, Callaghan, Australia.
  • Hooper SR Department of Allied Health Sciences, School of Medicine, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA.
  • Schoch K Department of Pediatrics, Division of Medical Genetics, Duke University School of Medicine, Durham, NC, USA.
  • Shashi V Department of Pediatrics, Division of Medical Genetics, Duke University School of Medicine, Durham, NC, USA.
  • Simon TJ MIND Institute and Department of Psychiatry and Behavioral Sciences, University of California Davis, Davis, CA, USA.
  • Tassone F Department of Microbiology and Molecular Medicine, University of California Davis, Davis, CA, USA.
  • Arango C Department of Child and Adolescent Psychiatry, Hospital General Universitario Gregorio Marañón, IiSGM, CIBERSAM, School of Medicine, Universidad Complutense, Madrid, Spain.
  • Fraguas D Department of Child and Adolescent Psychiatry, Hospital General Universitario Gregorio Marañón, IiSGM, CIBERSAM, School of Medicine, Universidad Complutense, Madrid, Spain.
  • García-Miñaúr S Institute of Medical and Molecular Genetics (INGEMM), La Paz University Hospital, Madrid, Spain.
  • Morey-Canyelles J Hospital Universitari Son Espases, Palma, Spain.
  • Rosell J Hospital Universitari Son Espases, Palma, Spain.
  • Suñer DH Laboratorio Unidad de Diagnóstico Molecular y Genética Clínica, Hospital Universitari Son Espases, Palma de Mallorca, Spain.
  • Raventos-Simic J Hospital Universitari Son Espases, Palma, Spain.
  • Epstein MP MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK. williamsnm@cardiff.ac.uk.
  • Williams NM Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, ON, Canada. anne.bassett@utoronto.ca.
  • Bassett AS
Show more…
  • 2020-02-05
Published in:
  • Molecular psychiatry. - 2020
Molecular Biology
Cellular and Molecular Neuroscience
Psychiatry and Mental health
English Schizophrenia occurs in about one in four individuals with 22q11.2 deletion syndrome (22q11.2DS). The aim of this International Brain and Behavior 22q11.2DS Consortium (IBBC) study was to identify genetic factors that contribute to schizophrenia, in addition to the ~20-fold increased risk conveyed by the 22q11.2 deletion. Using whole-genome sequencing data from 519 unrelated individuals with 22q11.2DS, we conducted genome-wide comparisons of common and rare variants between those with schizophrenia and those with no psychotic disorder at age ≥25 years. Available microarray data enabled direct comparison of polygenic risk for schizophrenia between 22q11.2DS and independent population samples with no 22q11.2 deletion, with and without schizophrenia (total n = 35,182). Polygenic risk for schizophrenia within 22q11.2DS was significantly greater for those with schizophrenia (padj = 6.73 × 10-6). Novel reciprocal case-control comparisons between the 22q11.2DS and population-based cohorts showed that polygenic risk score was significantly greater in individuals with psychotic illness, regardless of the presence of the 22q11.2 deletion. Within the 22q11.2DS cohort, results of gene-set analyses showed some support for rare variants affecting synaptic genes. No common or rare variants within the 22q11.2 deletion region were significantly associated with schizophrenia. These findings suggest that in addition to the deletion conferring a greatly increased risk to schizophrenia, the risk is higher when the 22q11.2 deletion and common polygenic risk factors that contribute to schizophrenia in the general population are both present.
Language
  • English
Open access status
green
Identifiers
Persistent URL
https://sonar.ch/global/documents/46886
Statistics
Document views: 22 File downloads:
  • fulltext.pdf: 0