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

GARY DONOHOE

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

GARY DONOHOE

Psychology

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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 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 (Î²â=ââ0.71 to â1.37; Pââ0.0005). In an independent sample, consistent results were obtained, with significant effects in the pallidum (Î²â=ââ0.95, Pâ=â0.0042). The two data sets combined showed significant negative dose-response for the accumbens, caudate, pallidum, putamen and ICV (Pâ=â0.0032, 8.9âÃâ10â6, 1.7âÃâ10â9, 3.5âÃâ10â12 and 1.0âÃâ10â4, 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.

Original language	English (Ireland)
Journal	Molecular Psychiatry
Volume	25
Issue number	3
Publication status	Published - 1 Jan 2020

Authors (Note for portal: view the doc link for the full list of authors)

Authors
SÃ¸nderby, Ida E.,GÃºstafsson, Ãmar,Doan, Nhat Trung,Hibar, Derrek P.,Martin-Brevet, Sandra,Abdellaoui, Abdel,Ames, David,Amunts, Katrin,Andersson, Michael,Armstrong, Nicola J.,Bernard, Manon,Blackburn, Nicholas,Blangero, John,Boomsma, Dorret I.,Bralten, Janita,Brattbak, Hans-Richard,Brodaty, Henry,Brouwer, Rachel M.,BÃ¼low, Robin,Calhoun, Vince,Caspers, Svenja,Cavalleri, Gianpiero,Chen, Chi-Hua,Cichon, Sven,Ciufolini, Simone,Corvin, Aiden,Crespo-Facorro, Benedicto,Curran, Joanne E.,Dale, Anders M.,Dalvie, Shareefa,Dazzan, Paola,de Geus, Eco J. C.,de Zubicaray, Greig I.,de Zwarte, Sonja M. C.,Delanty, Norman,den Braber, Anouk,DesriviÃ¨res, Sylvane,Donohoe, Gary,Draganski, Bogdan,Ehrlich, Stefan,Espeseth, Thomas,Fisher, Simon E.,Franke, Barbara,Frouin, Vincent,Fukunaga, Masaki,Gareau, Thomas,Glahn, David C.,Grabe, Hans,Groenewold, Nynke A.,Haavik, Jan,HÃ¥berg, Asta,Hashimoto, Ryota,Hehir-Kwa, Jayne Y.,Heinz, Andreas,Hillegers, Manon H. J.,Hoffmann, Per,Holleran, Laurena,Ikeda, Masashi

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

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 ({\^I}²{\^a}={\^a}{\^a}0.71 to {\^a}1.37; P{\^a}{\^a}0.0005). In an independent sample, consistent results were obtained, with significant effects in the pallidum ({\^I}²{\^a}={\^a}{\^a}0.95, P{\^a}={\^a}0.0042). The two data sets combined showed significant negative dose-response for the accumbens, caudate, pallidum, putamen and ICV (P{\^a}={\^a}0.0032, 8.9{\^a}{\~A}{\^a}10{\^a}6, 1.7{\^a}{\~A}{\^a}10{\^a}9, 3.5{\^a}{\~A}{\^a}10{\^a}12 and 1.0{\^a}{\~A}{\^a}10{\^a}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.",

author = "GARY DONOHOE",

year = "2020",

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language = "English (Ireland)",

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journal = "Molecular Psychiatry",

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T1 - Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia

AU - DONOHOE, GARY

PY - 2020/1/1

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N2 - 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 (Î²â=ââ0.71 to â1.37; Pââ0.0005). In an independent sample, consistent results were obtained, with significant effects in the pallidum (Î²â=ââ0.95, Pâ=â0.0042). The two data sets combined showed significant negative dose-response for the accumbens, caudate, pallidum, putamen and ICV (Pâ=â0.0032, 8.9âÃâ10â6, 1.7âÃâ10â9, 3.5âÃâ10â12 and 1.0âÃâ10â4, 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.

AB - 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 (Î²â=ââ0.71 to â1.37; Pââ0.0005). In an independent sample, consistent results were obtained, with significant effects in the pallidum (Î²â=ââ0.95, Pâ=â0.0042). The two data sets combined showed significant negative dose-response for the accumbens, caudate, pallidum, putamen and ICV (Pâ=â0.0032, 8.9âÃâ10â6, 1.7âÃâ10â9, 3.5âÃâ10â12 and 1.0âÃâ10â4, 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.

M3 - Article

VL - 25

JO - Molecular Psychiatry

JF - Molecular Psychiatry

IS - 3

ER -

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

Abstract

Authors (Note for portal: view the doc link for the full list of authors)

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