TY  - JOUR
AU  - Sonderby, I. E.
AU  - Gustafsson, O.
AU  - Doan, N. T.
AU  - Hibar, D. P.
AU  - Martin-Brevet, S.
AU  - Westley, L. T.
AU  - Jacquemont, S.
AU  - Djurovic, S.
AU  - Stefansson, H.
AU  - Stefansson, K.
AU  - Thompson, P. M.
AU  - Andreassen, O. A.
AU  - Cichon, Sven
TI  - Dose response of the 16p11.2 digital copy number on intracranial volume and basal ganglia
JO  - Molecular psychiatry
VL  - 25
SN  - 1359-4184
CY  - London
PB  - Macmillan
M1  - FZJ-2018-03605
SP  - 584–602
PY  - 2020
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.
LB  - PUB:(DE-HGF)16
C6  - pmid:30283035
UR  - <Go to ISI:>//WOS:000516569700011
DO  - DOI:10.1038/s41380-018-0118-1
UR  - https://juser.fz-juelich.de/record/848364
ER  -