TY - JOUR
T1 - Mutations associated with neuropsychiatric conditions delineate functional brain connectivity dimensions contributing to autism and schizophrenia
AU - Moreau, Clara A.
AU - Urchs, Sebastian G.W.
AU - Kuldeep, Kumar
AU - Orban, Pierre
AU - Schramm, Catherine
AU - Dumas, Guillaume
AU - Labbe, Aurélie
AU - Huguet, Guillaume
AU - Douard, Elise
AU - Quirion, Pierre Olivier
AU - Lin, Amy
AU - Kushan, Leila
AU - Grot, Stephanie
AU - Luck, David
AU - Mendrek, Adrianna
AU - Potvin, Stephane
AU - Stip, Emmanuel
AU - Bourgeron, Thomas
AU - Evans, Alan C.
AU - Bearden, Carrie E.
AU - Bellec, Pierre
AU - Jacquemont, Sebastien
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 16p11.2 and 22q11.2 Copy Number Variants (CNVs) confer high risk for Autism Spectrum Disorder (ASD), schizophrenia (SZ), and Attention-Deficit-Hyperactivity-Disorder (ADHD), but their impact on functional connectivity (FC) remains unclear. Here we report an analysis of resting-state FC using magnetic resonance imaging data from 101 CNV carriers, 755 individuals with idiopathic ASD, SZ, or ADHD and 1,072 controls. We characterize CNV FC-signatures and use them to identify dimensions contributing to complex idiopathic conditions. CNVs have large mirror effects on FC at the global and regional level. Thalamus, somatomotor, and posterior insula regions play a critical role in dysconnectivity shared across deletions, duplications, idiopathic ASD, SZ but not ADHD. Individuals with higher similarity to deletion FC-signatures exhibit worse cognitive and behavioral symptoms. Deletion similarities identified at the connectivity level could be related to the redundant associations observed genome-wide between gene expression spatial patterns and FC-signatures. Results may explain why many CNVs affect a similar range of neuropsychiatric symptoms.
AB - 16p11.2 and 22q11.2 Copy Number Variants (CNVs) confer high risk for Autism Spectrum Disorder (ASD), schizophrenia (SZ), and Attention-Deficit-Hyperactivity-Disorder (ADHD), but their impact on functional connectivity (FC) remains unclear. Here we report an analysis of resting-state FC using magnetic resonance imaging data from 101 CNV carriers, 755 individuals with idiopathic ASD, SZ, or ADHD and 1,072 controls. We characterize CNV FC-signatures and use them to identify dimensions contributing to complex idiopathic conditions. CNVs have large mirror effects on FC at the global and regional level. Thalamus, somatomotor, and posterior insula regions play a critical role in dysconnectivity shared across deletions, duplications, idiopathic ASD, SZ but not ADHD. Individuals with higher similarity to deletion FC-signatures exhibit worse cognitive and behavioral symptoms. Deletion similarities identified at the connectivity level could be related to the redundant associations observed genome-wide between gene expression spatial patterns and FC-signatures. Results may explain why many CNVs affect a similar range of neuropsychiatric symptoms.
UR - https://www.scopus.com/pages/publications/85092763274
U2 - 10.1038/s41467-020-18997-2
DO - 10.1038/s41467-020-18997-2
M3 - Article
C2 - 33077750
AN - SCOPUS:85092763274
SN - 2041-1723
VL - 11
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 5272
ER -