Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia
journal contributionposted on 04.05.2021, 14:01 by Ida Elken Sønderby, Gianpiero Cavalleri, Norman Delanty, Mark McCormack, Christopher D. Whelan
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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CommentsThe original article is available at https://www.nature.com/ This article has an Erratum that can be found at https://doi.org/10.1038/s41380-019-0358-8 Sønderby IE, et al. Correction: Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia. Molecular Psychiatry. 2020(3):692-695.
Published CitationSønderby IE, et al European Consortium, for the ENIGMA-CNV working group. Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia. Molecular Psychiatry. 2020(3):584-602.
Publication Date3 October 2018
- School of Pharmacy and Biomolecular Sciences
- Beaumont Hospital
- Neurological and Psychiatric Disorders
PublisherSpringer Nature Limited
- Published Version (Version of Record)
16p11.2 European Consortium, for the ENIGMA-CNV working groupPutamenChromosomes, Human, Pair 16Chromosome DisordersMagnetic Resonance ImagingAutistic DisorderSchizophreniaDNA Copy Number VariationsNeurodevelopmental DisordersPsychiatryBiological SciencesMedical and Health SciencesPsychology and Cognitive Sciences