Article
Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia
Author/s | Sønderby, Ida E.
Gústafsson, Ómar Doan, Nhat Trung Hibar, Derrek P. Martin-Brevet, Sandra Abdellaoui, Abdel Crespo Facorro, Benedicto ![]() ![]() ![]() ![]() ![]() ![]() ![]() Prieto, Carlos |
Department | Universidad de Sevilla. Departamento de Psiquiatría |
Publication Date | 2020 |
Deposit Date | 2023-04-05 |
Published in |
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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 ... 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. |
Funding agencies | NCRR NIH HHS NIBIB NIH HHS NICHD NIH HHS NIGMS NIH HHS NIMH NIH HHS |
Project ID. | R01 EB005846; R01 EB000840; U54 EB020403; R01 EB006841
![]() R01 EB005846; R01 EB000840; U54 EB020403; R01 EB006841 ![]() R01 HD050735 ![]() P20 GM103472 ![]() RC1 MH089257; RC2 MH089951; K08 MH068540; R01 MH078111; R01 MH085772; R01 MH081802; R01 MH083824; RC2 MH089995 ![]() |
Citation | Sønderby, I.E., Gústafsson, Ó., Doan, N.T., Hibar, D.P., Martin-Brevet, S., Abdellaoui, A.,...,Prieto, C. (2020). Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia. Molecular Psychiatry, 25 (3), 584-602. https://doi.org/10.1038/s41380-018-0118-1. |
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