Titre
Quantifying the Effects of 16p11.2 Copy Number Variants on Brain Structure: A Multisite Genetic-First Study.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Martin-Brevet, S.
Auteure/Auteur
Rodríguez-Herreros, B.
Auteure/Auteur
Nielsen, J.A.
Auteure/Auteur
Moreau, C.
Auteure/Auteur
Modenato, C.
Auteure/Auteur
Maillard, A.M.
Auteure/Auteur
Pain, A.
Auteure/Auteur
Richetin, S.
Auteure/Auteur
Jønch, A.E.
Auteure/Auteur
Qureshi, A.Y.
Auteure/Auteur
Zürcher, N.R.
Auteure/Auteur
Conus, P.
Auteure/Auteur
Chung, W.K.
Auteure/Auteur
Sherr, E.H.
Auteure/Auteur
Spiro, J.E.
Auteure/Auteur
Kherif, F.
Auteure/Auteur
Beckmann, J.S.
Auteure/Auteur
Hadjikhani, N.
Auteure/Auteur
Reymond, A.
Auteure/Auteur
Buckner, R.L.
Auteure/Auteur
Draganski, B.
Auteure/Auteur
Jacquemont, S.
Auteure/Auteur
Contributrices/contributeurs
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.
Groupes de travail
16p11.2 European Consortium
Simons Variation in Individuals Project (VIP) Consortium
Liens vers les unités
ISSN
1873-2402
Statut éditorial
Publié
Date de publication
2018-08-15
Volume
84
Numéro
4
Première page
253
Dernière page/numéro d’article
264
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
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.
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.
Sujets
PID Serval
serval:BIB_8964BF69CE74
PMID
Open Access
Oui
Date de création
2018-05-24T16:08:21.396Z
Date de création dans IRIS
2025-05-21T00:38:49Z
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Nom
29778275.pdf
Version du manuscrit
published
Licence
https://creativecommons.org/licenses/by-nc-nd/4.0
Taille
2.53 MB
Format
Adobe PDF
PID Serval
serval:BIB_8964BF69CE74.P001
URN
urn:nbn:ch:serval-BIB_8964BF69CE744
Somme de contrôle
(MD5):2d5dd5a93927c9558d22b1e7c48e60ea