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.

16p11.2 和 22q11.2 拷贝数变异 (CNV) 赋予自闭症谱系障碍 (ASD)、精神分裂症 (SZ) 和注意力缺陷多动障碍 (ADHD) 的高风险，但它们对功能连接 (FC) 的影响还不清楚。在此，我们报告了使用来自 101 名 CNV 携带者、755 名特发性 ASD、SZ 或 ADHD 患者以及 1,072 名对照者的磁共振成像数据对静息态 FC 进行的分析。我们描述了 CNV FC 特征，并使用它们来识别导致复杂特发性疾病的维度。CNV 在全球和区域层面对 FC 有很大的镜像效应。丘脑、躯体运动和后岛叶区域在缺失、重复、特发性自闭症谱系障碍、精神分裂症（但不是多动症）所共有的连接障碍中发挥着关键作用。与删除 FC 签名具有更高相似性的个体表现出更差的认知和行为症状。在连接水平上发现的删除相似性可能与在基因表达空间模式和 FC 特征之间观察到的全基因组冗余关联有关。结果可以解释为什么许多 CNV 会影响类似范围的神经精神症状。