Quantifying the Effects of 16p11.2 Copy Number Variants on Brain Structure: A Multisite Genetic-First Study.

Détails

Ressource 1Télécharger: 29778275.pdf (2594.18 [Ko])
Etat: Public
Version: Final published version
Licence: CC BY-NC-ND 4.0
ID Serval
serval:BIB_8964BF69CE74
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Quantifying the Effects of 16p11.2 Copy Number Variants on Brain Structure: A Multisite Genetic-First Study.
Périodique
Biological psychiatry
Auteur(s)
Martin-Brevet S., Rodríguez-Herreros B., Nielsen J.A., Moreau C., Modenato C., Maillard A.M., Pain A., Richetin S., Jønch A.E., Qureshi A.Y., Zürcher N.R., Conus P., Chung W.K., Sherr E.H., Spiro J.E., Kherif F., Beckmann J.S., Hadjikhani N., Reymond A., Buckner R.L., Draganski B., Jacquemont S.
Collaborateur(s)
16p11.2 European Consortium, Simons Variation in Individuals Project (VIP) Consortium
Contributeur(s)
Addor M.C., Andrieux J., Arveiler B., Baujat G., Sloan-Béna F., Belfiore M., Bonneau D., Bouquillon S., Boute O., Brusco A., Busa T., Caberg J.H., Campion D., Colombert V., Cordier M.P., David A., Debray F.G., Delrue M.A., Doco-Fenzy M., Dunkhase-Heinl U., Edery P., Fagerberg C., Faivre L., Forzano F., Genevieve D., Gérard M., Giachino D., Guichet A., Guillin O., Héron D., Isidor B., Jacquette A., Jaillard S., Journel H., Keren B., Lacombe D., Lebon S., Le Caignec C., Lemaître M.P., Lespinasse J., Mathieu-Dramart M., Mercier S., Mignot C., Missirian C., Petit F., Pilekær Sørensen K., Pinson L., Plessis G., Prieur F., Rooryck-Thambo C., Rossi M., Sanlaville D., Schlott Kristiansen B., Schluth-Bolard C., Till M., Van Haelst M., Van Maldergem L., Alupay H., Aaronson B., Ackerman S., Ankenman K., Anwar A., Atwell C., Bowe A., Beaudet A.L., Benedetti M., Berg J., Berman J., Berry L.N., Bibb A.L., Blaskey L., Brennan J., Brewton C.M., Buckner R., Bukshpun P., Burko J., Cali P., Cerban B., Chang Y., Cheong M., Chow V., Chu Z., Chudnovskaya D., Cornew L., Dale C., Dell J., Dempsey A.G., Deschamps T., Earl R., Edgar J., Elgin J., Olson J.E., Evans Y.L., Findlay A., Fischbach G.D., Fisk C., Fregeau B., Gaetz B., Gaetz L., Garza S., Gerdts J., Glenn O., Gobuty S.E., Golembski R., Greenup M., Heiken K., Hines K., Hinkley L., Jackson F.I., Jenkins J., Jeremy R.J., Johnson K., Kanne S.M., Kessler S., Khan S.Y., Ku M., Kuschner E., Laakman A.L., Lam P., Lasala M.W., Lee H., LaGuerre K., Levy S., Cavanagh A.L., Llorens A.V., Campe K.L., Luks T.L., Marco E.J., Martin S., Martin A.J., Marzano G., Masson C., McGovern K.E., McNally Keehn R., Miller D.T., Miller F.K., Moss T.J., Murray R., Nagarajan S.S., Nowell K.P., Owen J., Paal A.M., Packer A., Page P.Z., Paul B.M., Peters A., Peterson D., Poduri A., Pojman N.J., Porche K., Proud M.B., Qasmieh S., Ramocki M.B., Reilly B., Roberts TPL, Shaw D., Sinha T., Smith-Packard B., Gallagher A.S., Swarnakar V., Thieu T., Triantafallou C., Vaughan R., Wakahiro M., Wallace A., Ward T., Wenegrat J., Wolken A.
ISSN
1873-2402 (Electronic)
ISSN-L
0006-3223
Statut éditorial
Publié
Date de publication
15/08/2018
Peer-reviewed
Oui
Volume
84
Numéro
4
Pages
253-264
Langue
anglais
Notes
Publication types: Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
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.
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.
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.
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.
Mots-clé
Adolescent, Adult, Autism Spectrum Disorder/diagnostic imaging, Autism Spectrum Disorder/genetics, Brain/pathology, Child, Chromosome Deletion, Chromosome Duplication, Chromosomes, Human, Pair 16/genetics, Cognitive Dysfunction/diagnostic imaging, Cognitive Dysfunction/genetics, DNA Copy Number Variations, Female, Humans, Intellectual Disability/diagnostic imaging, Intellectual Disability/genetics, Language, Magnetic Resonance Imaging, Male, Middle Aged, Neurodevelopmental Disorders/diagnostic imaging, Neurodevelopmental Disorders/genetics, Schizophrenia/diagnostic imaging, Schizophrenia/genetics, Young Adult, 16p11.2, Autism spectrum disorder, Copy number variant, Genetics, Imaging, Neurodevelopmental disorders
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/05/2018 17:08
Dernière modification de la notice
09/10/2019 5:09
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