Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
QIMR Home Page
GenEpi Home Page
About GenEpi
Publications
Contacts
Research
Staff Index
Collaborators
Software Tools
Computing Resources
Studies
Search
GenEpi Intranet
PMID
33753722
TITLE
1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans.
ABSTRACT
Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers-the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.
DATE PUBLISHED
2021 03 22
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2020/11/26
accepted 2021/01/08
revised 2020/12/23
entrez 2021/03/23 06:25
pubmed 2021/03/24 06:00
medline 2021/06/29 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Sønderby IE Sønderby Ida E IE KG Jebsen Centre for Neurodevelopmental Disorders, University of Oslo, Oslo, Norway. i.e.sonderby@medisin.uio.no.
van der Meer D van der Meer Dennis D School of Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, the Netherlands.
Moreau C Moreau Clara C Centre de recherche de l'Institut universitaire de gériatrie de Montréal, Montreal, Quebec, Canada.
Kaufmann T Kaufmann Tobias T Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany.
Walters GB Walters G Bragi GB Faculty of Medicine, University of Iceland, Reykjavík, Iceland.
Ellegaard M Ellegaard Maria M Department of Clinical Biochemistry, Copenhagen University Hospital, Rigshospitalet, Glostrup, Denmark.
Abdellaoui A Abdellaoui Abdel A Department of Biological Psychology and Netherlands Twin Register, VU University Amsterdam, Amsterdam, the Netherlands.
Ames D Ames David D National Ageing Research Institute, Parkville, Australia.
Amunts K Amunts Katrin K C. and O. Vogt Institute for Brain Research, Medical Faculty, University Hospital Düsseldorf, Heinrich Heine University Duesseldorf, Düsseldorf, Germany.
Andersson M Andersson Micael M Department of Integrative Medical Biology, Umeå University, Umeå, Sweden.
Armstrong NJ Armstrong Nicola J NJ Mathematics and Statistics, Murdoch University, Perth, Australia.
Bernard M Bernard Manon M Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada.
Blackburn NB Blackburn Nicholas B NB South Texas Diabetes and Obesity Institute, Department of Human Genetics, School of Medicine, University of Texas Rio Grande Valley, Brownsville, USA.
Blangero J Blangero John J South Texas Diabetes and Obesity Institute, Department of Human Genetics, School of Medicine, University of Texas Rio Grande Valley, Brownsville, USA.
Boomsma DI Boomsma Dorret I DI Amsterdam Public Health Research Institute, VU Medical Center, Amsterdam, the Netherlands.
Brodaty H Brodaty Henry H Dementia Centre for Research Collaboration, School of Psychiatry, University of New South Wales, Sydney, Australia.
Brouwer RM Brouwer Rachel M RM Department of Psychiatry, University Medical Center Brain Center, Utrecht University, Utrecht, the Netherlands.
Bülow R Bülow Robin R Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany.
Bøen R Bøen Rune R Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
Cahn W Cahn Wiepke W Altrecht Science, Utrecht, the Netherlands.
Calhoun VD Calhoun Vince D VD The Department of Electrical and Computer Engineering, University of New Mexico, Albuquerque, USA.
Caspers S Caspers Svenja S Institute for Anatomy I, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
Ching CRK Ching Christopher R K CRK Imaging Genetics Center, Mark and Mary Stevens Institute for Neuroimaging and Informatics, University of Southern California, Los Angeles, USA.
Cichon S Cichon Sven S Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.
Ciufolini S Ciufolini Simone S Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
Crespo-Facorro B Crespo-Facorro Benedicto B University Hospital Virgen del Rocío, IBiS, Centre de Investigació Biomédica en Red Salud Mental (CIBERSAM), Sevilla, Spain.
Curran JE Curran Joanne E JE South Texas Diabetes and Obesity Institute, Department of Human Genetics, School of Medicine, University of Texas Rio Grande Valley, Brownsville, USA.
Dale AM Dale Anders M AM Center for Multimodal Imaging and Genetics, University of California, San Diego, USA.
Dalvie S Dalvie Shareefa S Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, Western Cape, South Africa.
Dazzan P Dazzan Paola P Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
de Geus EJC de Geus Eco J C EJC Amsterdam Public Health Research Institute, VU Medical Center, Amsterdam, the Netherlands.
de Zubicaray GI de Zubicaray Greig I GI Faculty of Health, Queensland University of Technology, Brisbane, Australia.
de Zwarte SMC de Zwarte Sonja M C SMC Department of Psychiatry, University Medical Center Brain Center, Utrecht University, Utrecht, the Netherlands.
Desrivieres S Desrivieres Sylvane S Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
Doherty JL Doherty Joanne L JL Cardiff University Brain Research Imaging Centre School of Psychology, Cardiff University, Cardiff, United Kingdom.
Donohoe G Donohoe Gary G Centre for Neuroimaging and Cognitive Genomics, School of Psychology and Discipline of Biochemistry, National University of Ireland Galway, Galway, Ireland.
Draganski B Draganski Bogdan B Neurology Department, Max-Planck-Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.
Ehrlich S Ehrlich Stefan S Division of Psychological and Social Medicine, Faculty of Medicine, TU Dresden, Dresden, Germany.
Eising E Eising Else E Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, the Netherlands.
Espeseth T Espeseth Thomas T Bjørknes College, Oslo, Norway.
Fejgin K Fejgin Kim K Signal Transduction, H. Lundbeck A/S, Ottiliavej 9, DK-2500, Valby, Denmark.
Fisher SE Fisher Simon E SE Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, the Netherlands.
Fladby T Fladby Tormod T Institute of Clinical Medicine, Campus Ahus, University of Oslo, Oslo, Norway.
Frei O Frei Oleksandr O NORMENT, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Frouin V Frouin Vincent V Université Paris-Saclay, CEA, Neurospin, 91191, Gif-sur-Yvette, France.
Fukunaga M Fukunaga Masaki M Department of Life Science, Sokendai, Hayama, Japan.
Gareau T Gareau Thomas T Université Paris-Saclay, CEA, Neurospin, 91191, Gif-sur-Yvette, France.
Ge T Ge Tian T Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Glahn DC Glahn David C DC Harvard Medical School, Boston, Massachusetts, USA.
Grabe HJ Grabe Hans J HJ German Center of Neurodegenerative Diseases (DZNE), Rostock/Greifswald, Greifswald, Germany.
Groenewold NA Groenewold Nynke A NA Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, Western Cape, South Africa.
Gústafsson Ó Gústafsson Ómar Ó deCODE Genetics (Amgen), Reykjavík, Iceland.
Haavik J Haavik Jan J Division of Psychiatry, Haukeland University Hospital, Bergen, Norway.
Haberg AK Haberg Asta K AK St Olav's Hospital, Department of Radiology and Nuclear Medicine, Trondheim, Norway.
Hall J Hall Jeremy J School of Medicine, Cardiff University, Cardiff, United Kingdom.
Hashimoto R Hashimoto Ryota R Osaka University, Osaka, Japan.
Hehir-Kwa JY Hehir-Kwa Jayne Y JY Princess Màxima Center for Pediatric Oncology, Utrecht, the Netherlands.
Hibar DP Hibar Derrek P DP Genentech, Inc., South San Francisco, 94080, CA, USA.
Hillegers MHJ Hillegers Manon H J MHJ Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC-Sophia, Rotterdam, the Netherlands.
Hoffmann P Hoffmann Per P Institute of Human Genetics, University of Bonn Medical School, Bonn, Germany.
Holleran L Holleran Laurena L Centre for Neuroimaging and Cognitive Genomics, School of Psychology and Discipline of Biochemistry, National University of Ireland Galway, Galway, Ireland.
Holmes AJ Holmes Avram J AJ Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
Homuth G Homuth Georg G Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
Hottenga JJ Hottenga Jouke-Jan JJ Amsterdam Public Health Research Institute, VU Medical Center, Amsterdam, the Netherlands.
Hulshoff Pol HE Hulshoff Pol Hilleke E HE Department of Psychiatry, University Medical Center Brain Center, Utrecht University, Utrecht, the Netherlands.
Ikeda M Ikeda Masashi M Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Japan.
Jahanshad N Jahanshad Neda N Imaging Genetics Center, Mark and Mary Stevens Institute for Neuroimaging and Informatics, University of Southern California, Los Angeles, USA.
Jockwitz C Jockwitz Christiane C Institute for Anatomy I, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
Johansson S Johansson Stefan S Department of Medical Genetics, Haukeland University Hospital, Bergen, Norway.
Jönsson EG Jönsson Erik G EG Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Jørgensen NR Jørgensen Niklas R NR Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Kikuchi M Kikuchi Masataka M Department of Genome Informatics, Graduate School of Medicine, Osaka University, Osaka, Japan.
Knowles EEM Knowles Emma E M EEM Harvard Medical School, Boston, Massachusetts, USA.
Kumar K Kumar Kuldeep K Sainte Justine Hospital Research Center, Montreal, Quebec, Canada.
Le Hellard S Le Hellard Stephanie S Dr Einar Martens Research Group for Biological Psychiatry, Department of Medical Genetics, Haukeland University Hospital, Bergen, Norway.
Leu C Leu Costin C Chalfont Centre for Epilepsy, Chalfont-St-Peter, United Kingdom.
Linden DEJ Linden David E J DEJ MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, United Kingdom.
Liu J Liu Jingyu J Tri-institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia State University, Georgia Institute of Technology, Emory University, Atlanta, USA.
Lundervold A Lundervold Arvid A Mohn Medical Imaging and Visualization Centre, Department of Radiology, Haukeland University Hospital, Bergen, Norway.
Lundervold AJ Lundervold Astri Johansen AJ Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway.
Maillard AM Maillard Anne M AM Service des Troubles du Spectre de l'Autisme et apparentés, Lausanne University Hospital, Lausanne, Switzerland.
Martin NG Martin Nicholas G NG Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Martin-Brevet S Martin-Brevet Sandra S Laboratory for Research in Neuroimaging LREN, Centre for Research in Neurosciences, Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Mather KA Mather Karen A KA Neuroscience Research Australia, Randwick, Australia.
Mathias SR Mathias Samuel R SR Harvard Medical School, Boston, Massachusetts, USA.
McMahon KL McMahon Katie L KL Herston Imaging Research Facility and School of Clinical Sciences, Queensland University of Technology, Brisbane, Australia.
McRae AF McRae Allan F AF Queensland Brain Institute, University of Queensland, Brisbane, Australia.
Medland SE Medland Sarah E SE Psychiatric Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Meyer-Lindenberg A Meyer-Lindenberg Andreas A Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Moberget T Moberget Torgeir T Department of Psychology, University of Oslo, Oslo, Norway.
Modenato C Modenato Claudia C University of Lausanne, Lausanne, Switzerland.
Sánchez JM Sánchez Jennifer Monereo JM School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands.
Morris DW Morris Derek W DW Centre for Neuroimaging and Cognitive Genomics, School of Psychology and Discipline of Biochemistry, National University of Ireland Galway, Galway, Ireland.
Mühleisen TW Mühleisen Thomas W TW Department of Biomedicine, University of Basel, Basel, Switzerland.
Murray RM Murray Robin M RM Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
Nielsen J Nielsen Jacob J Signal Transduction, H. Lundbeck A/S, Ottiliavej 9, DK-2500, Valby, Denmark.
Nordvik JE Nordvik Jan E JE The CatoSenteret Rehabilitation Center, Son, Norway.
Nyberg L Nyberg Lars L Department of Radiation Sciences, Umeå University, Umeå, Sweden.
Loohuis LMO Loohuis Loes M Olde LMO Center for Neurobehavioral Genetics, University of California, Los Angeles, USA.
Ophoff RA Ophoff Roel A RA Department of Psychiatry, Erasmus University Medical Center, Rotterdam, The Netherlands.
Owen MJ Owen Michael J MJ MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, United Kingdom.
Paus T Paus Tomas T Physiology and Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada.
Pausova Z Pausova Zdenka Z Physiology and Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada.
Peralta JM Peralta Juan M JM South Texas Diabetes and Obesity Institute, Department of Human Genetics, School of Medicine, University of Texas Rio Grande Valley, Brownsville, USA.
Pike GB Pike G Bruce GB Departments of Radiology and Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada.
Prieto C Prieto Carlos C Bioinformatics Service, Nucleus, University of Salamanca, Salamanca, Spain.
Quinlan EB Quinlan Erin B EB Centre for Population Neuroscience and Precision Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
Reinbold CS Reinbold Céline S CS Department of Psychology, University of Oslo, Oslo, Norway.
Marques TR Marques Tiago Reis TR Psychiatric Imaging Group, MRC London Institute of Medical Sciences (LMS), Hammersmith Hospital, Imperial College, London, United Kingdom.
Rucker JJH Rucker James J H JJH Institute of Psychiatry, Psychology and Neuroscience, London, London, United Kingdom.
Sachdev PS Sachdev Perminder S PS Neuropsychiatric Institute, The Prince of Wales Hospital, Sydney, Australia.
Sando SB Sando Sigrid B SB University Hospital of Trondheim,Department of Neurology and Clinical Neurophysiology, Trondheim, Norway.
Schofield PR Schofield Peter R PR School of Medical Sciences, University of New South Wales, Sydney, Australia.
Schork AJ Schork Andrew J AJ The Translational Genetics Institute (TGEN), Phoenix, AZ, United States.
Schumann G Schumann Gunter G Centre for Population Neuroscience and Precision Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
Shin J Shin Jean J Physiology and Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada.
Shumskaya E Shumskaya Elena E Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Silva AI Silva Ana I AI Cardiff University Brain Research Imaging Centre School of Psychology, Cardiff University, Cardiff, United Kingdom.
Sisodiya SM Sisodiya Sanjay M SM Chalfont Centre for Epilepsy, Chalfont-St-Peter, United Kingdom.
Steen VM Steen Vidar M VM Dr Einar Martens Research Group for Biological Psychiatry, Department of Medical Genetics, Haukeland University Hospital, Bergen, Norway.
Stein DJ Stein Dan J DJ South African Medical Research Council Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
Strike LT Strike Lachlan T LT Queensland Brain Institute, University of Queensland, Brisbane, Australia.
Suzuki IK Suzuki Ikuo K IK The University of Tokyo, Department of Biological Sciences, Graduate School of Science, Tokyo, Japan.
Tamnes CK Tamnes Christian K CK Department of Psychiatry, Diakonhjemmet Hospital, Oslo, Norway.
Teumer A Teumer Alexander A Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
Thalamuthu A Thalamuthu Anbupalam A Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia.
Tordesillas-Gutiérrez D Tordesillas-Gutiérrez Diana D Department of Radiology, Marqués de Valdecilla University Hospital, Valdecilla Biomedical Research Institute IDIVAL, Santander, Spain.
Uhlmann A Uhlmann Anne A Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, Western Cape, South Africa.
Ulfarsson MO Ulfarsson Magnus O MO Faculty of Electrical and Computer Engineering, University of Iceland, Reykjavík, Iceland.
van 't Ent D van 't Ent Dennis D Amsterdam Neuroscience, Amsterdam, the Netherlands.
van den Bree MBM van den Bree Marianne B M MBM School of Medicine, Cardiff University, Cardiff, United Kingdom.
Vanderhaeghen P Vanderhaeghen Pierre P Université Libre de Bruxelles (U.L.B.), Institut de Recherches en Biologie Humaine et Moléculaire (IRIBHM), and ULB Neuroscience Institute (UNI), 1070, Brussels, Belgium.
Vassos E Vassos Evangelos E National Institute for Health Research, Mental Health Biomedical Research Centre, South London and Maudsley National Health Service Foundation Trust and King's College London, London, United Kingdom.
Wen W Wen Wei W Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia.
Wittfeld K Wittfeld Katharina K German Center of Neurodegenerative Diseases (DZNE), Rostock/Greifswald, Greifswald, Germany.
Wright MJ Wright Margaret J MJ Centre for Advanced Imaging, University of Queensland, Brisbane, Australia.
Agartz I Agartz Ingrid I Department of Psychiatry, Diakonhjemmet Hospital, Oslo, Norway.
Djurovic S Djurovic Srdjan S Norwegian Centre for Mental Disorders Research, Department of Clinical Science, University of Bergen, Bergen, Norway.
Westlye LT Westlye Lars T LT Department of Psychology, University of Oslo, Oslo, Norway.
Stefansson H Stefansson Hreinn H deCODE Genetics (Amgen), Reykjavík, Iceland.
Stefansson K Stefansson Kari K Faculty of Medicine, University of Iceland, Reykjavík, Iceland.
Jacquemont S Jacquemont Sébastien S Department of Pediatrics, University of Montreal, Montreal, Quebec, Canada.
Thompson PM Thompson Paul M PM Imaging Genetics Center, Mark and Mary Stevens Institute for Neuroimaging and Informatics, University of Southern California, Los Angeles, USA.
Andreassen OA Andreassen Ole A OA NORMENT, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
ENIGMA-CNV working group
INVESTIGATORS
LASTNAME FORENAME INITIALS AFFILIATION
van der Meer Dennis D
de Geus Eco J C EJC
de Zubicaray Greig I GI
de Zwarte Sonja M C SMC
Le Hellard Stephanie S
van 't Ent Dennis D
van den Bree Marianne B M MBM
JOURNAL
VOLUME: 11
ISSUE: 1
TITLE: Translational psychiatry
ISOABBREVIATION: Transl Psychiatry
YEAR: 2021
MONTH: 03
DAY: 22
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 2158-3188
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Transl Psychiatry
COUNTRY: United States
ISSNLINKING: 2158-3188
NLMUNIQUEID: 101562664
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
GRANTS
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Brain diagnostic imaging
Chromosome Deletion diagnostic imaging
Cognition diagnostic imaging
DNA Copy Number Variations diagnostic imaging
Female diagnostic imaging
Humans diagnostic imaging
Male diagnostic imaging
Schizophrenia genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
Designed by: GenEpi IT
Maintained by: GenEpi IT
Feedback: webmaster
Copyright © 2007 QIMR
For more information Contact Us
epiit@qimr.edu.au
Last Modified: Oct 15 2007