Copy number variations (CNVs) are implicated across many neurodevelopmental disorders (NDDs) and contribute to their shared genetic etiology. Multiple studies have attempted to identify shared etiology among NDDs, but this is the first genome-wide CNV analysis across autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), schizophrenia (SCZ), and obsessive-compulsive disorder (OCD) at once. Using microarray (Affymetrix CytoScan HD), we genotyped 2,691 subjects diagnosed with an NDD (204 SCZ, 1,838 ASD, 427 ADHD and 222 OCD) and 1,769 family members, mainly parents. We identified rare CNVs, defined as those found in <0.1% of 10,851 population control samples. We found clinically relevant CNVs (broadly defined) in 284 (10.5%) of total subjects, including 22 (10.8%) among subjects with SCZ, 209 (11.4%) with ASD, 40 (9.4%) with ADHD, and 13 (5.6%) with OCD. Among all NDD subjects, we identified 17 (0.63%) with aneuploidies and 115 (4.3%) with known genomic disorder variants. We searched further for genes impacted by different CNVs in multiple disorders. Examples of NDD-associated genes linked across more than one disorder (listed in order of occurrence frequency) are NRXN1, SEH1L, LDLRAD4, GNAL, GNG13, MKRN1, DCTN2, KNDC1, PCMTD2, KIF5A, SYNM, and long non-coding RNAs: AK127244 and PTCHD1-AS. We demonstrated that CNVs impacting the same genes could potentially contribute to the etiology of multiple NDDs. The CNVs identified will serve as a useful resource for both research and diagnostic laboratories for prioritization of variants.

拷贝数变异（CNV）涉及许多神经发育障碍（NDD），并有助于其共同的遗传病因。多项研究已尝试鉴定NDD之间共享的病因，但这是首次针对自闭症谱系障碍（ASD），注意力缺陷多动障碍（ADHD），精神分裂症（SCZ）和强迫症（OCD）的全基因组CNV分析立刻。使用微阵列芯片（Affymetrix CytoScan HD），我们对诊断为NDD（204 SCZ，1,838 ASD，427 ADHD和222 OCD）的2,691名受试者和1769名家庭成员（主要是父母）进行了基因分型。我们确定了罕见的CNV，其定义为在10,851个人口对照样品中不到0.1％的CNV。我们在284名（10.5％）的受试者中发现了与临床相关的CNV（广泛定义），其中SCZ受试者中有22名（10.8％），ASD受试者中有209名（11.4％），40名（9。ADHD占4％），OCD占13（5.6％）。在所有NDD受试者中，我们鉴定出17个（0.63％）具有非整倍性和115个（4.3％）具有已知的基因组疾病变体。我们进一步搜索了多种疾病中受不同CNV影响的基因。跨不止一种疾病（按发生频率顺序列出）的与NDD相关的基因的例子如下：NRXN1，SEH1L，LDLRAD4，GNAL，GNG13，MKRN1，DCTN2，KNDC1，PCMTD2，KIF5A，SYNM和长非编码RNAs：AK127244和PTCHD1-AS。我们证明了影响相同基因的CNV可能会导致多种NDD的病因。所确定的CNV将为研究实验室和诊断实验室提供有用的资源，帮助他们确定变体的优先级。