TY - JOUR
T1 - Effects of eight neuropsychiatric copy number variants on human brain structure
AU - 16p11.2 European Consortium
AU - Simons Searchlight Consortium
AU - Modenato, Claudia
AU - Kumar, Kuldeep
AU - Moreau, Clara
AU - Martin-Brevet, Sandra
AU - Huguet, Guillaume
AU - Schramm, Catherine
AU - Jean-Louis, Martineau
AU - Martin, Charles Olivier
AU - Younis, Nadine
AU - Tamer, Petra
AU - Douard, Elise
AU - Thébault-Dagher, Fanny
AU - Côté, Valérie
AU - Charlebois, Audrey Rose
AU - Deguire, Florence
AU - Maillard, Anne M.
AU - Rodriguez-Herreros, Borja
AU - Pain, Aurèlie
AU - Richetin, Sonia
AU - Addor, Marie Claude
AU - Andrieux, Joris
AU - Arveiler, Benoît
AU - Baujat, Geneviève
AU - Sloan-Béna, Frédérique
AU - Belfiore, Marco
AU - Bonneau, Dominique
AU - Bouquillon, Sonia
AU - Boute, Odile
AU - Brusco, Alfredo
AU - Busa, Tiffany
AU - Caberg, Jean Hubert
AU - Campion, Dominique
AU - Colombert, Vanessa
AU - Cordier, Marie Pierre
AU - David, Albert
AU - Debray, François Guillaume
AU - Delrue, Marie Ange
AU - Doco-Fenzy, Martine
AU - Dunkhase-Heinl, Ulrike
AU - Edery, Patrick
AU - Fagerberg, Christina
AU - Faivre, Laurence
AU - Forzano, Francesca
AU - Genevieve, David
AU - Gérard, Marion
AU - Giachino, Daniela
AU - Guichet, Agnès
AU - Guillin, Olivier
AU - Héron, Delphine
AU - Aaronson, Benjamin
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - Many copy number variants (CNVs) confer risk for the same range of neurodevelopmental symptoms and psychiatric conditions including autism and schizophrenia. Yet, to date neuroimaging studies have typically been carried out one mutation at a time, showing that CNVs have large effects on brain anatomy. Here, we aimed to characterize and quantify the distinct brain morphometry effects and latent dimensions across 8 neuropsychiatric CNVs. We analyzed T1-weighted MRI data from clinically and non-clinically ascertained CNV carriers (deletion/duplication) at the 1q21.1 (n = 39/28), 16p11.2 (n = 87/78), 22q11.2 (n = 75/30), and 15q11.2 (n = 72/76) loci as well as 1296 non-carriers (controls). Case-control contrasts of all examined genomic loci demonstrated effects on brain anatomy, with deletions and duplications showing mirror effects at the global and regional levels. Although CNVs mainly showed distinct brain patterns, principal component analysis (PCA) loaded subsets of CNVs on two latent brain dimensions, which explained 32 and 29% of the variance of the 8 Cohen’s d maps. The cingulate gyrus, insula, supplementary motor cortex, and cerebellum were identified by PCA and multi-view pattern learning as top regions contributing to latent dimension shared across subsets of CNVs. The large proportion of distinct CNV effects on brain morphology may explain the small neuroimaging effect sizes reported in polygenic psychiatric conditions. Nevertheless, latent gene brain morphology dimensions will help subgroup the rapidly expanding landscape of neuropsychiatric variants and dissect the heterogeneity of idiopathic conditions.
AB - Many copy number variants (CNVs) confer risk for the same range of neurodevelopmental symptoms and psychiatric conditions including autism and schizophrenia. Yet, to date neuroimaging studies have typically been carried out one mutation at a time, showing that CNVs have large effects on brain anatomy. Here, we aimed to characterize and quantify the distinct brain morphometry effects and latent dimensions across 8 neuropsychiatric CNVs. We analyzed T1-weighted MRI data from clinically and non-clinically ascertained CNV carriers (deletion/duplication) at the 1q21.1 (n = 39/28), 16p11.2 (n = 87/78), 22q11.2 (n = 75/30), and 15q11.2 (n = 72/76) loci as well as 1296 non-carriers (controls). Case-control contrasts of all examined genomic loci demonstrated effects on brain anatomy, with deletions and duplications showing mirror effects at the global and regional levels. Although CNVs mainly showed distinct brain patterns, principal component analysis (PCA) loaded subsets of CNVs on two latent brain dimensions, which explained 32 and 29% of the variance of the 8 Cohen’s d maps. The cingulate gyrus, insula, supplementary motor cortex, and cerebellum were identified by PCA and multi-view pattern learning as top regions contributing to latent dimension shared across subsets of CNVs. The large proportion of distinct CNV effects on brain morphology may explain the small neuroimaging effect sizes reported in polygenic psychiatric conditions. Nevertheless, latent gene brain morphology dimensions will help subgroup the rapidly expanding landscape of neuropsychiatric variants and dissect the heterogeneity of idiopathic conditions.
UR - http://www.scopus.com/inward/record.url?scp=85111690086&partnerID=8YFLogxK
U2 - 10.1038/s41398-021-01490-9
DO - 10.1038/s41398-021-01490-9
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C2 - 34285187
AN - SCOPUS:85111690086
SN - 2158-3188
VL - 11
JO - Translational Psychiatry
JF - Translational Psychiatry
IS - 1
M1 - 399
ER -