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

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Sonderby, IE, Gustafsson, O, Doan, NT, Hibar, DP, Martin-Brevet, S, Abdellaoui, A, Ames, D, Amunts, K, Andersson, M, Armstrong, NJ, Bernard, M, Blackburn, NB ORCID: 0000-0002-9774-1539, Blangero, J, Boomsma, DI, Bralten, J, Brattbak, H-R, Brodaty, H, Brouwe, RM, Bulow, R, Calhoun, V, Caspers, S, Cavalleri, G, Chen, C-H, Cichon, S, Ciufolini, S, Corvin, A, Crespo-Facorro, B, Curran, JE, Dale, AM, Dalvie, S, Dazzan, P, de Geus, EJC, de Zubicaray, GI, de Zwarte, SMC, Delanty, N, den Braber, A, Desrivieres, S, Donohoe, G, Draganski, B, Ehrlich, S, Espeseth, T, Fisher, SE, Franke, B, Frouin, V, Fukunaga, M, Hashimoto, R, Hehir-Kwa, JY, Heinz, A, Hillegers, MHJ, Hoffmann, P, Holleran, L, Hottenga, J-J, Hulshoff, HE, Ikeda, M, Jahanshad, N, Jernigan, T, Jockwitz, C, Johansson, S, Jonsdottir, GA, Jonsson, EG, Kahn, R, Kaufmann, T, Kelly, S, Kikuchi, M, Knowles, EEM, Kolskar, KK, Kwok, JB, Le Hellard, S, Leu, C, Liu, J, Lundervold, AJ, Lundervold, A, Martin, NG, Mather, K, Mathias, SR, McCormack, M, McMahon, KL, McRae, A, Milaneschi, Y, Moreau, C, Morris, D, Mothersill, D, Muhleisen, TW, Murray, R, Nordvik, JE, Nyberg, L, Loohuis, LMO, Ophoff, R, Paus, T, Pausova, Z, Penninx, B, Peralta, JM, Pike, B, Prieto, C, Pudas, S, Quinlan, E, Quintana, DS, Reinbold, CS, Reis Marques, T, Reymond, A, Richard, G, Rodriguez-Herreros, B, Roiz-Santianez, R, Rokicki, J, Rucker, J, Sachdev, P, Sanders, A-M, Sando, SB, Schmaal, L, Schofield, PR, Schork, AJ, Schumann, G, Shin, J, Shumskaya, E, Sisodiya, S, Steen, VM, Stein, DJ, Steinberg, S, Strike, L, Teumer, A, Thalamuthu, A, Tordesillas-Gutierrez, D, Turner, J, Ueland, T, Uhlmann, A, Ulfarsson, MO, van 't En, D, van der Meer, D, van Haren, NEM, Vaskinn, A, Vassos, E, Walters, GB, Wang, Y, Wen, W, Whelan, CD, Wittfeld, K, Wright, M, Yamamori, H, Zayats, T, Agartz, I, Westlye, LT, Jacquemont, S, Djurovic, S, Stefansson, H, Stefansson, K, Thompson, P and Andreassen, OA 2020 , 'Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia' , Molecular Psychiatry, vol. 25, no. 3 , pp. 584-602 , doi: 10.1038/s41380-018-0118-1.

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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 subcorticalbrain volumes of 12 16p11.2 distal deletion and 12 duplication carriers to 6882 non-carriers from the large-scale brainMagnetic Resonance Imaging collaboration, ENIGMA-CNV. After stringent CNV calling procedures, and standardizedFreeSurfer image analysis, we found negative dose-response associations with copy number on intracranial volume and onregional caudate, pallidum and putamen volumes (β = −0.71 to −1.37; P β = −0.95, P = 0.0042). The two data sets combined showedsignificant 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 noncarriers. This is the first brain MRI study of the impact of the 16p11.2 distal CNV, and we demonstrate a specific effect onsubcortical brain structures, suggesting a neuropathological pattern underlying the neurodevelopmental syndromes.

Item Type: Article
Authors/Creators:Sonderby, IE and Gustafsson, O and Doan, NT and Hibar, DP and Martin-Brevet, S and Abdellaoui, A and Ames, D and Amunts, K and Andersson, M and Armstrong, NJ and Bernard, M and Blackburn, NB and Blangero, J and Boomsma, DI and Bralten, J and Brattbak, H-R and Brodaty, H and Brouwe, RM and Bulow, R and Calhoun, V and Caspers, S and Cavalleri, G and Chen, C-H and Cichon, S and Ciufolini, S and Corvin, A and Crespo-Facorro, B and Curran, JE and Dale, AM and Dalvie, S and Dazzan, P and de Geus, EJC and de Zubicaray, GI and de Zwarte, SMC and Delanty, N and den Braber, A and Desrivieres, S and Donohoe, G and Draganski, B and Ehrlich, S and Espeseth, T and Fisher, SE and Franke, B and Frouin, V and Fukunaga, M and Hashimoto, R and Hehir-Kwa, JY and Heinz, A and Hillegers, MHJ and Hoffmann, P and Holleran, L and Hottenga, J-J and Hulshoff, HE and Ikeda, M and Jahanshad, N and Jernigan, T and Jockwitz, C and Johansson, S and Jonsdottir, GA and Jonsson, EG and Kahn, R and Kaufmann, T and Kelly, S and Kikuchi, M and Knowles, EEM and Kolskar, KK and Kwok, JB and Le Hellard, S and Leu, C and Liu, J and Lundervold, AJ and Lundervold, A and Martin, NG and Mather, K and Mathias, SR and McCormack, M and McMahon, KL and McRae, A and Milaneschi, Y and Moreau, C and Morris, D and Mothersill, D and Muhleisen, TW and Murray, R and Nordvik, JE and Nyberg, L and Loohuis, LMO and Ophoff, R and Paus, T and Pausova, Z and Penninx, B and Peralta, JM and Pike, B and Prieto, C and Pudas, S and Quinlan, E and Quintana, DS and Reinbold, CS and Reis Marques, T and Reymond, A and Richard, G and Rodriguez-Herreros, B and Roiz-Santianez, R and Rokicki, J and Rucker, J and Sachdev, P and Sanders, A-M and Sando, SB and Schmaal, L and Schofield, PR and Schork, AJ and Schumann, G and Shin, J and Shumskaya, E and Sisodiya, S and Steen, VM and Stein, DJ and Steinberg, S and Strike, L and Teumer, A and Thalamuthu, A and Tordesillas-Gutierrez, D and Turner, J and Ueland, T and Uhlmann, A and Ulfarsson, MO and van 't En, D and van der Meer, D and van Haren, NEM and Vaskinn, A and Vassos, E and Walters, GB and Wang, Y and Wen, W and Whelan, CD and Wittfeld, K and Wright, M and Yamamori, H and Zayats, T and Agartz, I and Westlye, LT and Jacquemont, S and Djurovic, S and Stefansson, H and Stefansson, K and Thompson, P and Andreassen, OA
Keywords: brain morphology, copy number variations
Journal or Publication Title: Molecular Psychiatry
Publisher: Nature Publishing Group
ISSN: 1359-4184
DOI / ID Number: 10.1038/s41380-018-0118-1
Copyright Information:

Copyright 2018 The Authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/

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