TY - JOUR
T1 - Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia
AU - Sønderby, Ida Elken
AU - Gústafsson, Ómar
AU - Doan, Nhat Trung
AU - Hibar, Derrek Paul
AU - Martin-Brevet, Sandra
AU - Westlye, Lars T.
AU - Jacquemont, Sébastien
AU - Djurovic, Srdjan
AU - Stefánsson, Hreinn
AU - Stefánsson, Kari
AU - Thompson, Paul M.
AU - Andreassen, Ole A.
AU - Abdellaoui, A.
AU - Boomsma, D.I.
AU - de Geus, Eco JC
AU - den Braber, A.
AU - Hottenga, J.J.
AU - W J H Penninx, Brenda
AU - Milaneschi, Yuri
AU - van t Ent, D.
AU - ENIGMA-CNV working group
PY - 2020/3
Y1 - 2020/3
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 (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.
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 (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.
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U2 - 10.1038/s41380-018-0118-1
DO - 10.1038/s41380-018-0118-1
M3 - Article
AN - SCOPUS:85054383956
SN - 1359-4184
VL - 25
SP - 584
EP - 602
JO - Molecular Psychiatry
JF - Molecular Psychiatry
ER -
