Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia.

Sønderby, I.E.; Gústafsson, Ó.; Doan, N.T.; Hibar, D.P.; Martin-Brevet, S.; Abdellaoui, A.; Ames, D.; Amunts, K.; Andersson, M.; Armstrong, N.J.; Bernard, M.; Blackburn, N.; Blangero, J.; Boomsma, D.I.; Bralten, J.; Brattbak, H.R.; Brodaty, H.; Brouwer, R.M.; Bülow, R.; Calhoun, V.; Caspers, S.; Cavalleri, G.; Chen, C.H.; Cichon, S.; Ciufolini, S.; Corvin, A.; Crespo-Facorro, B.; Curran, J.E.; Dale, A.M.; Dalvie, S.; Dazzan, P.; de Geus, EJC; de Zubicaray, G.I.; de Zwarte, SMC; Delanty, N.; den Braber, A.; Desrivières, S.; Donohoe, G.; Draganski, B.; Ehrlich, S.; Espeseth, T.; Fisher, S.E.; Franke, B.; Frouin, V.; Fukunaga, M.; Gareau, T.; Glahn, D.C.; Grabe, H.; Groenewold, N.A.; Haavik, J.; Håberg, A.; Hashimoto, R.; Hehir-Kwa, J.Y.; Heinz, A.; Hillegers, MHJ; Hoffmann, P.; Holleran, L.; Hottenga, J.J.; Hulshoff, H.E.; Ikeda, M.; Jahanshad, N.; Jernigan, T.; Jockwitz, C.; Johansson, S.; Jonsdottir, G.A.; Jönsson, E.G.; Kahn, R.; Kaufmann, T.; Kelly, S.; Kikuchi, M.; Knowles, EEM; Kolskår, K.K.; Kwok, J.B.; Hellard, S.L.; Leu, C.; Liu, J.; Lundervold, A.J.; Lundervold, A.; Martin, N.G.; Mather, K.; Mathias, S.R.; McCormack, M.; McMahon, K.L.; McRae, A.; Milaneschi, Y.; Moreau, C.; Morris, D.; Mothersill, D.; Mühleisen, T.W.; Murray, R.; Nordvik, J.E.; Nyberg, L.; Olde Loohuis, L.M.; Ophoff, R.; Paus, T.; Pausova, Z.; Penninx, B.; Peralta, J.M.; Pike, B.; Prieto, C.; Pudas, S.; Quinlan, E.; Quintana, D.S.; Reinbold, C.S.; Marques, T.R.; Reymond, A.; Richard, G.; Rodriguez-Herreros, B.; Roiz-Santiañez, R.; Rokicki, J.; Rucker, J.; Sachdev, P.; Sanders, A.M.; Sando, S.B.; Schmaal, L.; Schofield, P.R.; Schork, A.J.; Schumann, G.; Shin, J.; Shumskaya, E.; Sisodiya, S.; Steen, V.M.; Stein, D.J.; Steinberg, S.; Strike, L.; Teumer, A.; Thalamuthu, A.; Tordesillas-Gutierrez, D.; Turner, J.; Ueland, T.; Uhlmann, A.; Ulfarsson, M.O.; van 't Ent, D.; van der Meer, D.; van Haren, NEM; Vaskinn, A.; Vassos, E.; Walters, G.B.; Wang, Y.; Wen, W.; Whelan, C.D.; Wittfeld, K.; Wright, M.; Yamamori, H.; Zayats, T.; Agartz, I.; Westlye, L.T.; Jacquemont, S.; Djurovic, S.; Stefánsson, H.; Stefánsson, K.; Thompson, P.; Andreassen, O.A.

doi:10.1038/s41380-018-0118-1

Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia.

Details

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Version: Final published version
License: CC BY 4.0

Serval ID

serval:BIB_8D048DECAD90

Type

Article: article from journal or magazin.

Collection

Publications

Institution

UNIL/CHUV

Title

Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia.

Journal

Molecular psychiatry

Author(s)

Sønderby I.E., Gústafsson Ó., Doan N.T., Hibar D.P., Martin-Brevet S., Abdellaoui A., Ames D., Amunts K., Andersson M., Armstrong N.J., Bernard M., Blackburn N., Blangero J., Boomsma D.I., Bralten J., Brattbak H.R., Brodaty H., Brouwer R.M., Bülow R., Calhoun V., Caspers S., Cavalleri G., Chen C.H., Cichon S., Ciufolini S., Corvin A., Crespo-Facorro B., Curran J.E., Dale A.M., Dalvie S., Dazzan P., de Geus EJC, de Zubicaray G.I., de Zwarte SMC, Delanty N., den Braber A., Desrivières S., Donohoe G., Draganski B., Ehrlich S., Espeseth T., Fisher S.E., Franke B., Frouin V., Fukunaga M., Gareau T., Glahn D.C., Grabe H., Groenewold N.A., Haavik J., Håberg A., Hashimoto R., Hehir-Kwa J.Y., Heinz A., Hillegers MHJ, Hoffmann P., Holleran L., Hottenga J.J., Hulshoff H.E., Ikeda M., Jahanshad N., Jernigan T., Jockwitz C., Johansson S., Jonsdottir G.A., Jönsson E.G., Kahn R., Kaufmann T., Kelly S., Kikuchi M., Knowles EEM, Kolskår K.K., Kwok J.B., Hellard S.L., Leu C., Liu J., Lundervold A.J., Lundervold A., Martin N.G., Mather K., Mathias S.R., McCormack M., McMahon K.L., McRae A., Milaneschi Y., Moreau C., Morris D., Mothersill D., Mühleisen T.W., Murray R., Nordvik J.E., Nyberg L., Olde Loohuis L.M., Ophoff R., Paus T., Pausova Z., Penninx B., Peralta J.M., Pike B., Prieto C., Pudas S., Quinlan E., Quintana D.S., Reinbold C.S., Marques T.R., Reymond A., Richard G., Rodriguez-Herreros B., Roiz-Santiañez R., Rokicki J., Rucker J., Sachdev P., Sanders A.M., Sando S.B., Schmaal L., Schofield P.R., Schork A.J., Schumann G., Shin J., Shumskaya E., Sisodiya S., Steen V.M., Stein D.J., Steinberg S., Strike L., Teumer A., Thalamuthu A., Tordesillas-Gutierrez D., Turner J., Ueland T., Uhlmann A., Ulfarsson M.O., van 't Ent D., van der Meer D., van Haren NEM, Vaskinn A., Vassos E., Walters G.B., Wang Y., Wen W., Whelan C.D., Wittfeld K., Wright M., Yamamori H., Zayats T., Agartz I., Westlye L.T., Jacquemont S., Djurovic S., Stefánsson H., Stefánsson K., Thompson P., Andreassen O.A.

Working group(s)

16p11.2 European Consortium, for the ENIGMA-CNV working group

ISSN

1476-5578 (Electronic)

ISSN-L

1359-4184

Publication state

Published

Issued date

03/2020

Peer-reviewed

Oui

Volume

Number

Pages

584-602

Language

english

Notes

Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish

Abstract

Carriers of large recurrent copy number variants (CNVs) have a higher risk of developing neurodevelopmental disorders. The 16p11.2 distal CNV predisposes carriers to e.g., autism spectrum disorder and schizophrenia. We compared subcortical brain volumes of 12 16p11.2 distal deletion and 12 duplication carriers to 6882 non-carriers from the large-scale brain Magnetic Resonance Imaging collaboration, ENIGMA-CNV. After stringent CNV calling procedures, and standardized FreeSurfer image analysis, we found negative dose-response associations with copy number on intracranial volume and on regional caudate, pallidum and putamen volumes (β = -0.71 to -1.37; P < 0.0005). In an independent sample, consistent results were obtained, with significant effects in the pallidum (β = -0.95, P = 0.0042). The two data sets combined showed significant negative dose-response for the accumbens, caudate, pallidum, putamen and ICV (P = 0.0032, 8.9 × 10 -6 , 1.7 × 10 - 9 , 3.5 × 10 -12 and 1.0 × 10 -4 , respectively). Full scale IQ was lower in both deletion and duplication carriers compared to non-carriers. This is the first brain MRI study of the impact of the 16p11.2 distal CNV, and we demonstrate a specific effect on subcortical brain structures, suggesting a neuropathological pattern underlying the neurodevelopmental syndromes.

URN

urn:nbn:ch:serval-BIB_8D048DECAD901

OAI-PMH

oai:serval.unil.ch:BIB_8D048DECAD90

DOI

10.1038/s41380-018-0118-1

Pubmed

30283035

Web of science

000516569700011

Open Access

Yes