School of Medicine Publications and Presentations
Document Type
Article
Publication Date
3-2020
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 (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 noncarriers. 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.
Recommended Citation
Sønderby, I.E., Gústafsson, Ó., Doan, N.T. et al. Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia. Mol Psychiatry 25, 584–602 (2020). https://doi.org/10.1038/s41380-018-0118-1
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Publication Title
Molecular Psychiatry
DOI
10.1038/s41380-018-0118-1
Academic Level
faculty
Mentor/PI Department
Office of Human Genetics
Comments
© The Author(s) 2018.