Evidence map›Paper›PMID 31665216›Full record

ArticleJAMA psychiatry2020

Association of Copy Number Variation of the 15q11.2 BP1-BP2 Region With Cortical and Subcortical Morphology and Cognition.

Writing Committee for the ENIGMA-CNV Working Group, Dennis van der Meer, Ida E Sønderby, Tobias Kaufmann, G Bragi Walters, Abdel Abdellaoui, David Ames, Katrin Amunts, Micael Andersson, Nicola J Armstrong and 123 more

Open access · hybridAbstract read
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In one paragraph

Article in JAMA psychiatry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed, 4 pooled it
8.2field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

55 citing papers in PubMed, 4 syntheses or guidelines pooled it, 90 citations in OpenAlex.

  1. Pooled it
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  12. Mapping Cerebellar Morphology in 15q11.2 CNV Carriers Using Normative Modeling.medRxiv : the preprint server for health sciences · 2025
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  20. Molecular signatures of cortical expansion in the human fetal brain.bioRxiv : the preprint server for biology · 2024
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

133 authors at 20 institutions in 16 countries.

Writing Committee for the ENIGMA-CNV Working Group
Dennis van der MeerNorwegian Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Ida E SønderbyNorwegian Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Tobias KaufmannNorwegian Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
G Bragi WaltersdeCODE Genetics, Reykjavík, Iceland.
Abdel AbdellaouiDepartment of Psychiatry, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
David AmesUniversity of Melbourne Academic Unit for Psychiatry of Old Age, Kew, Australia.
Katrin AmuntsInstitute of Neuroscience and Medicine, Research Centre Juelich, Juelich, Germany.
Micael AnderssonUmeå Centre for Functional Brain Imaging, Umeå University, Umeå, Sweden.
Nicola J ArmstrongMathematics and Statistics, Murdoch University, Perth, Australia.
Manon BernardResearch Institute, Hospital for Sick Children, Toronto, Ontario, Canada.
Nicholas B BlackburnSouth Texas Diabetes and Obesity Institute, Department of Human Genetics, School of Medicine, University of Texas Rio Grande Valley, Brownsville.
John BlangeroSouth Texas Diabetes and Obesity Institute, Department of Human Genetics, School of Medicine, University of Texas Rio Grande Valley, Brownsville.
Dorret I BoomsmaDepartment of Biological Psychology and Netherlands Twin Register, VU University Amsterdam, Amsterdam, the Netherlands.
Henry BrodatyCentre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia.
Rachel M BrouwerDepartment of Psychiatry, UMC Brain Center, University Medical Center Utrecht, Utrecht, the Netherlands.
Robin BülowDepartment of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany.
Wiepke CahnDepartment of Psychiatry, UMC Brain Center, University Medical Center Utrecht, Utrecht, the Netherlands.
Vince D CalhounTri-institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia State University, Georgia Institute of Technology, Emory University, Atlanta.
Svenja CaspersInstitute of Neuroscience and Medicine, Research Centre Juelich, Juelich, Germany.
Gianpiero L CavalleriThe School of Pharmacy and Biomolecular Sciences, The Royal College of Surgeons in Ireland, Dublin, Ireland.
Christopher R K ChingInterdepartmental Neuroscience Program, University of California, Los Angeles.
Sven CichonInstitute of Neuroscience and Medicine, Research Centre Juelich, Juelich, Germany.
Simone CiufoliniDepartment of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
Aiden CorvinDepartment of Psychiatry and Neuropsychiatric Genetics Research Group, Institute of Molecular Medicine, Trinity College Dublin, Dublin, Ireland.
Benedicto Crespo-FacorroUniversity Hospital Marqués de Valdecilla, IdahoIVAL, Centre de Investigación Biomédica en Red Salud Mental (CIBERSAM), Santander, Spain.
Joanne E CurranSouth Texas Diabetes and Obesity Institute, Department of Human Genetics, School of Medicine, University of Texas Rio Grande Valley, Brownsville.
Shareefa DalvieDepartment of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, Western Cape, South Africa.
Paola DazzanDepartment of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
Eco J C de GeusDepartment of Biological Psychology and Netherlands Twin Register, VU University Amsterdam, Amsterdam, the Netherlands.
Greig I de ZubicarayFaculty of Health and Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia.
Sonja M C de ZwarteDepartment of Psychiatry, UMC Brain Center, University Medical Center Utrecht, Utrecht, the Netherlands.
Norman DelantyThe SFI FutureNeuro Research Centre, Dublin, Ireland.
Anouk den BraberDepartment of Biological Psychology and Netherlands Twin Register, VU University Amsterdam, Amsterdam, the Netherlands.
Sylvane DesrivieresInstitute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
Marta Di FortiInstitute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
Joanne L DohertyMRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, United Kingdom.
Gary DonohoeCentre for Neuroimaging and Cognitive Genomics, School of Psychology and Discipline of Biochemistry, National University of Ireland Galway, Galway, Ireland.
Stefan EhrlichPsychological and Social Medicine, Faculty of Medicine, Dresden University of Technology, Dresden, Germany.
Else EisingLanguage and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, the Netherlands.
Thomas EspesethDepartment of Psychology, University of Oslo, Oslo, Norway.
Simon E FisherLanguage and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, the Netherlands.
Tormod FladbyAkershus University Hospital, Lorenskog, Norway.
Oleksandr FreiNorwegian Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Vincent FrouinNeurospin, Le Commissariat à l'énergie atomique et aux énergies alternatives, Université Paris-Saclay, Gif-sur-Yvette, France.
Masaki FukunagaDivision of Cerebral Integration, National Institute for Physiological Sciences, Okazaki, Japan.
Thomas GareauNeurospin, Le Commissariat à l'énergie atomique et aux énergies alternatives, Université Paris-Saclay, Gif-sur-Yvette, France.
David C GlahnBoston Children's Hospital, Boston, Massachusetts.
Hans J GrabeDepartment of Psychiatry and Psychotherapy, Greifswald, Germany.
Nynke A GroenewoldDepartment of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, Western Cape, South Africa.
Ómar GústafssondeCODE Genetics, Reykjavík, Iceland.
Jan HaavikDepartment of Biomedicine, University of Bergen, Bergen, Norway.
Asta K HabergDepartment of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway.
Ryota HashimotoDepartment of Pathology of Mental Diseases, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira, Japan.
Jayne Y Hehir-KwaPrincess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
Derrek P HibarGenentech, San Francisco, California.
Manon H J HillegersDepartment of Child and Adolescent Psychiatry/Psychology, Erasmus MC-Sophia's Children's Hospital, Rotterdam, the Netherlands.
Per HoffmannInstitute of Human Genetics, University of Bonn Medical School, Bonn, Germany.
Laurena HolleranCentre for Neuroimaging and Cognitive Genomics, School of Psychology and Discipline of Biochemistry, National University of Ireland Galway, Galway, Ireland.
Jouke-Jan HottengaDepartment of Biological Psychology and Netherlands Twin Register, VU University Amsterdam, Amsterdam, the Netherlands.
Hilleke E Hulshoff PolDepartment of Psychiatry, UMC Brain Center, University Medical Center Utrecht, Utrecht, the Netherlands.
Masashi IkedaDepartment of Psychiatry, Fujita Health University School of Medicine, Toyoake, Japan.
Sébastien JacquemontSainte Justine Hospital Research Center, Montreal, Quebec, Canada.
Neda JahanshadImaging Genetics Center, Mark and Mary Stevens Institute for Neuroimaging and Informatics, University of Southern California, Los Angeles.
Christiane JockwitzInstitute of Neuroscience and Medicine, Research Centre Juelich, Juelich, Germany.
Stefan JohanssonDepartment of Clinical Science, University of Bergen, Bergen, Norway.
Erik G JönssonNorwegian Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Masataka KikuchiDepartment of Genome Informatics, Graduate School of Medicine, Osaka University, Osaka, Japan.
Emma E M KnowlesBoston Children's Hospital, Boston, Massachusetts.
John B KwokThe University of Sydney Central Clinical School, Sydney, Australia.
Stephanie Le HellardNorwegian Centre for Mental Disorders Research, Department of Clinical Science, University of Bergen, Bergen, Norway.
David E J LindenSchool of Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, the Netherlands.
Jingyu LiuTri-institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia State University, Georgia Institute of Technology, Emory University, Atlanta.
Arvid LundervoldDepartment of Biomedicine, University of Bergen, Bergen, Norway.
Astri J LundervoldDepartment of Biological and Medical Psychology, University of Bergen, Bergen, Norway.
Nicholas G MartinGenetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Karen A MatherCentre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia.
Samuel R MathiasBoston Children's Hospital, Boston, Massachusetts.
Katie L McMahonHerston Imaging Research Facility and School of Clinical Sciences, Queensland University of Technology, Brisbane, Australia.
Allan F McRaeInstitute for Molecular Bioscience, University of Queensland, Brisbane, Australia.
Sarah E MedlandPsychiatric Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Torgeir MobergetNorwegian Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Clara MoreauSainte Justine Hospital Research Center, Montreal, Quebec, Canada.
Derek W MorrisCentre for Neuroimaging and Cognitive Genomics, School of Psychology and Discipline of Biochemistry, National University of Ireland Galway, Galway, Ireland.
Thomas W MühleisenInstitute of Neuroscience and Medicine, Research Centre Juelich, Juelich, Germany.
Robin M MurrayInstitute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
Jan E NordvikThe CatoSenteret Rehabilitation Center, Son, Norway.
Lars NybergUmeå Centre for Functional Brain Imaging, Umeå University, Umeå, Sweden.
Loes M Olde LoohuisCenter for Neurobehavioral Genetics, University of California, Los Angeles.
Roel A OphoffCenter for Neurobehavioral Genetics, University of California, Los Angeles.
Michael J OwenMRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, United Kingdom.
Tomas PausBloorview Research Institute, Holland Bloorview Kids Rehabilitation Hospital, Toronto, Ontario, Canada.
Zdenka PausovaResearch Institute, Hospital for Sick Children, Toronto, Ontario, Canada.
Juan M PeraltaSouth Texas Diabetes and Obesity Institute, Department of Human Genetics, School of Medicine, University of Texas Rio Grande Valley, Brownsville.
Bruce PikeDepartment of Radiology, University of Calgary, Calgary, Alberta, Canada.
Carlos PrietoBioinformatics Service, Nucleus, University of Salamanca, Salamanca, Spain.
Erin Burke QuinlanCentre for Population Neuroscience and Precision Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
Céline S ReinboldDepartment of Biomedicine, University of Basel, Basel, Switzerland.
Tiago Reis MarquesDepartment of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
James J H RuckerInstitute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
Perminder S SachdevCentre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia.
Sigrid B SandoDepartment of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway.
Peter R SchofieldSchool of Medical Sciences, University of New South Wales, Sydney, Australia.
Andrew J SchorkInstitute for Biological Psychiatry, Roskilde, Denmark.
Gunter SchumannCentre for Population Neuroscience and Precision Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
Jean ShinResearch Institute, Hospital for Sick Children, Toronto, Ontario, Canada.
Elena ShumskayaDonders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, the Netherlands.
Ana I SilvaCardiff University Brain Research Imaging Centre School of Psychology, Cardiff University, Cardiff, United Kingdom.
Sanjay M SisodiyaDepartment of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology and Chalfont Centre for Epilepsy, London, United Kingdom.
Vidar M SteenNorwegian Centre for Mental Disorders Research, Department of Clinical Science, University of Bergen, Bergen, Norway.
Dan J SteinDepartment of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, Western Cape, South Africa.
Lachlan T StrikeQueensland Brain Institute, The University of Queensland, Brisbane, Australia.
Christian K TamnesNorwegian Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Alexander TeumerInstitute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
Anbupalam ThalamuthuCentre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia.
Diana Tordesillas-GutiérrezNeuroimaging Unit, Technological Facilities, Valdecilla Biomedical Research Institute, IdahoIVAL, Santander, Spain.
Anne UhlmannDepartment of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, Western Cape, South Africa.
Magnús Ö ÚlfarssondeCODE Genetics, Reykjavík, Iceland.
Dennis van 't EntDepartment of Biological Psychology and Netherlands Twin Register, VU University Amsterdam, Amsterdam, the Netherlands.
Marianne B M van den BreeMRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, United Kingdom.
Evangelos VassosInstitute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
Wei WenCentre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia.
Katharina WittfeldDepartment of Psychiatry and Psychotherapy, Greifswald, Germany.
Margaret J WrightQueensland Brain Institute, The University of Queensland, Brisbane, Australia.
Tetyana ZayatsDepartment of Biomedicine, University of Bergen, Bergen, Norway.
Anders M DaleCenter for Multimodal Imaging and Genetics, University of California, San Diego.
Srdjan DjurovicNorwegian Centre for Mental Disorders Research, Department of Clinical Science, University of Bergen, Bergen, Norway.
Ingrid AgartzNorwegian Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Lars T WestlyeNorwegian Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Hreinn StefánssondeCODE Genetics, Reykjavík, Iceland.
Kári StefánssondeCODE Genetics, Reykjavík, Iceland.
Paul M ThompsonImaging Genetics Center, Mark and Mary Stevens Institute for Neuroimaging and Informatics, University of Southern California, Los Angeles.
Ole A AndreassenNorwegian Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
King's College London · GBOslo University Hospital · NOCardiff University · GBHaukeland University Hospital · NOdeCODE Genetics (Iceland) · ISThe University of Texas Rio Grande Valley · USUniversitätsmedizin Greifswald · DEUniversity Medical Center Utrecht · NLUniversity of Cape Town · ZAUniversity of Oslo · NOUNSW Sydney · AUOllscoil na Gaillimhe – University of Galway · IEThe University of Queensland · AUUniversity of Bergen · NOUniversity of California, Los Angeles · USAmsterdam Neuroscience · NLAmsterdam UMC Location Vrije Universiteit Amsterdam · NLAmsterdam University Medical Centers · NLCentre Hospitalier Universitaire Sainte-Justine · CAHarvard University · US

Funding

Training U54EB020403 · NIBIB · UNIVERSITY OF SOUTHERN CALIFORNIA · PI THOMPSON, PAUL M · 2014 to 2018
$10.1M
ENIGMA-SD: Understanding Sex Differences in Global Mental Health through ENIGMAR01MH116147 · NIMH · UNIVERSITY OF SOUTHERN CALIFORNIA · PI THOMPSON, PAUL M · 2018 to 2021
$2.5M
Training in the Multiscale and Multimodal Analysis of Biomarkers in Alzheimer’s DiseaseT32AG058507 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ARTHUR W TOGA · 2018 to 2026
$2.1M
ENIGMA World Aging CenterR56AG058854 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI THOMPSON, PAUL M · 2018 to 2018
$683k
Department of Health CS-2017-17-007Medical Research Council MC_PC_17228Medical Research Council MC_QA137853Medical Research Council MR/L010305/1Medical Research Council MR/N000390/1NIA NIH HHS R56 AG058854NIA NIH HHS T32 AG058507NIBIB NIH HHS U54 EB020403NIMH NIH HHS R01 MH116147
6 · The paper itself

Abstract

Importance: Recurrent microdeletions and duplications in the genomic region 15q11.2 between breakpoints 1 (BP1) and 2 (BP2) are associated with neurodevelopmental disorders. These structural variants are present in 0.5% to 1.0% of the population, making 15q11.2 BP1-BP2 the site of the most prevalent known pathogenic copy number variation (CNV). It is unknown to what extent this CNV influences brain structure and affects cognitive abilities. Objective: To determine the association of the 15q11.2 BP1-BP2 deletion and duplication CNVs with cortical and subcortical brain morphology and cognitive task performance. Design, Setting, and Participants: In this genetic association study, T1-weighted brain magnetic resonance imaging were combined with genetic data from the ENIGMA-CNV consortium and the UK Biobank, with a replication cohort from Iceland. In total, 203 deletion carriers, 45 247 noncarriers, and 306 duplication carriers were included. Data were collected from August 2015 to April 2019, and data were analyzed from September 2018 to September 2019. Main Outcomes and Measures: The associations of the CNV with global and regional measures of surface area and cortical thickness as well as subcortical volumes were investigated, correcting for age, age2, sex, scanner, and intracranial volume. Additionally, measures of cognitive ability were analyzed in the full UK Biobank cohort. Results: Of 45 756 included individuals, the mean (SD) age was 55.8 (18.3) years, and 23 754 (51.9%) were female. Compared with noncarriers, deletion carriers had a lower surface area (Cohen d = -0.41; SE, 0.08; P = 4.9 × 10-8), thicker cortex (Cohen d = 0.36; SE, 0.07; P = 1.3 × 10-7), and a smaller nucleus accumbens (Cohen d = -0.27; SE, 0.07; P = 7.3 × 10-5). There was also a significant negative dose response on cortical thickness (β = -0.24; SE, 0.05; P = 6.8 × 10-7). Regional cortical analyses showed a localization of the effects to the frontal, cingulate, and parietal lobes. Further, cognitive ability was lower for deletion carriers compared with noncarriers on 5 of 7 tasks. Conclusions and Relevance: These findings, from the largest CNV neuroimaging study to date, provide evidence that 15q11.2 BP1-BP2 structural variation is associated with brain morphology and cognition, with deletion carriers being particularly affected. The pattern of results fits with known molecular functions of genes in the 15q11.2 BP1-BP2 region and suggests involvement of these genes in neuronal plasticity. These neurobiological effects likely contribute to the association of this CNV with neurodevelopmental disorders.

Indexed as

CognitionBrain Cortical ThicknessCerebral CortexChromosome BreakpointsChromosomes, Human, Pair 15DNA Copy Number VariationsFemaleGenetic Association StudiesHeterozygoteHumansMagnetic Resonance ImagingMaleMiddle AgedNeuroimagingNeuropsychological TestsOrgan Size

Identifiers

PMID31665216
PMCPMC6822096
OpenAlexW2982381555

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.