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  Quantifying the effects of 16p11.2 copy number variants on brain structure: A multisite genetic-first study

Martin-Brevet, S., Rodríguez-Herreros, B., Nielsen, J. A., Moreau, C., Modenato, C., Maillard, A. M., et al. (2018). Quantifying the effects of 16p11.2 copy number variants on brain structure: A multisite genetic-first study. Biological Psychiatry, 84(4), 253-264. doi:10.1016/j.biopsych.2018.02.1176.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0001-6AE8-3 Version Permalink: http://hdl.handle.net/21.11116/0000-0003-9CE5-B
Genre: Journal Article

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 Creators:
Martin-Brevet, Sandra1, 2, Author
Rodríguez-Herreros, Borja1, 3, Author
Nielsen, Jared A.4, 5, 6, Author
Moreau, Clara3, Author
Modenato, Claudia1, 2, Author
Maillard, Anne M.1, 7, Author
Pain, Aurélie1, 7, Author
Richetin, Sonia1, Author
Jønch, Aia E.3, 8, 9, Author
Qureshi, Abid Y.5, 10, Author
Zürcher, Nicole R.11, Author
Conus, Philippe12, Author
Chung, Wendy K.13, 14, Author
Sherr, Elliott H.15, Author
Spiro, John E.13, Author
Kherif, Ferath2, Author
Beckmann, Jacques S.1, Author
Hadjikhani, Nouchine11, 16, Author
Reymond, Alexandre17, Author
Buckner, Randy L.4, 5, 6, 11, Author
Draganski, Bogdan2, 18, Author              Jacquemont, Sébastien1, 3, Author16p11.2 European Consortium, Author              Simons Variation in Individuals Project (VIP) Consortium, Author               more..
Affiliations:
1Service of Medical Genetics, Centre hospitalier universitaire vaudois, Lausanne, Switzerland, ou_persistent22              
2Département des Neurosciences Cliniques, Laboratoire de Recherche en Neuroimagerie (LREN), Centre hospitalier universitaire vaudois, Lausanne, Switzerland, ou_persistent22              
3CHU Sainte-Justine Research Center, University of Montréal, QC, Canada, ou_persistent22              
4Department of Psychology, Harvard University, Cambridge, MA, USA, ou_persistent22              
5Center for Brain Science, Harvard University, Cambridge, MA, USA, ou_persistent22              
6Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA, ou_persistent22              
7Centre cantonal autisme (CCA), Centre hospitalier universitaire vaudois, Lausanne, Switzerland, ou_persistent22              
8Department of Clinical Genetics, Odense University Hospital (OUH), Denmark, ou_persistent22              
9Human Genetics, Department of Clinical Research, University of Southern Denmark, Odense, Denmark, ou_persistent22              
10Department of Neurology, University of Kansas Medical Center (KUMC), Kansas City, KS, USA, ou_persistent22              
11Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA, USA, ou_persistent22              
12Department of Psychiatry, Centre hospitalier universitaire vaudois, Lausanne, Switzerland, ou_persistent22              
13Simons Foundation, New York, NY, USA, ou_persistent22              
14Department of Pediatrics, Columbia University in the City of New York, NY, USA, ou_persistent22              
15Department of Neurology, University of California, San Francisco, CA, USA, ou_persistent22              
16Gillberg Neuropsychiatry Centre, Sahlgrenska Academy, University of Gothenburg, Sweden, ou_persistent22              
17Center for Integrative Genomics, University of Lausanne, Switzerland, ou_persistent22              
18Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_634549              

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Free keywords: 16p11.2; Autism spectrum disorder; Copy number variant; Genetics; Imaging; Neurodevelopmental disorders
 Abstract: Background: 16p11.2 breakpoint 4 to 5 copy number variants (CNVs) increase the risk for developing autism spectrum disorder, schizophrenia, and language and cognitive impairment. In this multisite study, we aimed to quantify the effect of 16p11.2 CNVs on brain structure. Methods: Using voxel- and surface-based brain morphometric methods, we analyzed structural magnetic resonance imaging collected at seven sites from 78 individuals with a deletion, 71 individuals with a duplication, and 212 individuals without a CNV. Results: Beyond the 16p11.2-related mirror effect on global brain morphometry, we observe regional mirror differences in the insula (deletion > control > duplication). Other regions are preferentially affected by either the deletion or the duplication: the calcarine cortex and transverse temporal gyrus (deletion > control; Cohen's d > 1), the superior and middle temporal gyri (deletion < control; Cohen's d < −1), and the caudate and hippocampus (control > duplication; −0.5 > Cohen's d > −1). Measures of cognition, language, and social responsiveness and the presence of psychiatric diagnoses do not influence these results. Conclusions: The global and regional effects on brain morphometry due to 16p11.2 CNVs generalize across site, computational method, age, and sex. Effect sizes on neuroimaging and cognitive traits are comparable. Findings partially overlap with results of meta-analyses performed across psychiatric disorders. However, the lack of correlation between morphometric and clinical measures suggests that CNV-associated brain changes contribute to clinical manifestations but require additional factors for the development of the disorder. These findings highlight the power of genetic risk factors as a complement to studying groups defined by behavioral criteria.

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Language(s): eng - English
 Dates: 2018-02-012017-10-182018-02-282018-03-272018-08-15
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1016/j.biopsych.2018.02.1176
PMID: 29778275
Other: Epub 2018
 Degree: -

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Project name : -
Grant ID : SFARI219193 ; SFARI274424
Funding program : -
Funding organization : Simons Foundation
Project name : -
Grant ID : -
Funding program : Bursary Professor Fellowship
Funding organization : Swiss National Science Foundation
Project name : -
Grant ID : 31003A160203
Funding program : -
Funding organization : Swiss National Science Foundation
Project name : -
Grant ID : CRSII33-133044
Funding program : Sinergia Grant
Funding organization : Swiss National Science Foundation
Project name : NCCR Synapsy
Grant ID : 32003B_159780
Funding program : -
Funding organization : Swiss National Science Foundation
Project name : -
Grant ID : -
Funding program : -
Funding organization : Foundation Parkinson Switzerland
Project name : -
Grant ID : -
Funding program : -
Funding organization : Foundation Synapsis
Project name : The Human Brain Project / HBP
Grant ID : 604102
Funding program : Funding Programme 7
Funding organization : European Commission (EC)
Project name : -
Grant ID : -
Funding program : -
Funding organization : Roger De Spoelberch and Partridge Foundations
Project name : -
Grant ID : -
Funding program : -
Funding organization : Jeanne et Jean Louis Levesque Foundation

Source 1

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Title: Biological Psychiatry
  Other : Biol. Psychiatry
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: New York : Elsevier
Pages: - Volume / Issue: 84 (4) Sequence Number: - Start / End Page: 253 - 264 Identifier: ISSN: 0006-3223
CoNE: https://pure.mpg.de/cone/journals/resource/954925384111