Comparative Analyses of Copy-Number Variation in Autism Spectrum Disorder and Schizophrenia Reveal Etiological Overlap and Biological Insights
Comparative Analyses of Copy-Number Variation in Autism Spectrum Disorder and Schizophrenia Reveal Etiological Overlap and Biological Insights
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DOI：
10.1016/j.celrep.2018.08.022
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发表时间：
2018-09-11
期刊：
影响因子：
8.8
通讯作者：
Ozaki, Norio
中科院分区：
文献类型：
--
作者：
Kushima, Itaru;Aleksic, Branko;Ozaki, Norio
在高加索人群中令人信服的证据表明，拷贝数变异(CNV)在自闭症谱系障碍(ASD)和精神分裂症(SCZ)中起着作用。我们分析了1,108例ASD病例，2,458例SCZ病例和2,095例对照，证实在这两种疾病中罕见外显子CNV的负担增加。在ASD和SCZ患者中，约有8%的患者发现有临床意义的(或致病的)CNV，包括这两种疾病共有的29个基因位点的CNV，这一比例显著高于对照组。表型分析揭示了具有临床意义的CNV与智力残疾之间的关联。基因集分析显示，在这两种疾病中，包括氧化应激反应、脂质代谢/修饰和基因组完整性在内的生物途径显著重叠。最后，基于生物信息学分析，我们在8个已知的ASD/SCZ相关CNV基因座(如22q11.2、3q29)中发现了多个与疾病相关的基因。我们的发现表明ASD和SCZ在病因上存在重叠，并为这些疾病提供了生物学上的见解。
Compelling evidence in Caucasian populations suggests a role for copy-number variations (CNVs) in autism spectrum disorder (ASD) and schizophrenia (SCZ). We analyzed 1,108 ASD cases, 2,458 SCZ cases, and 2,095 controls in a Japanese population and confirmed an increased burden of rare exonic CNVs in both disorders. Clinically significant (or pathogenic) CNVs, including those at 29 loci common to both disorders, were found in about 8% of ASD and SCZ cases, which was significantly higher than in controls. Phenotypic analysis revealed an association between clinically significant CNVs and intellectual disability. Gene set analysis showed significant over-lap of biological pathways in both disorders including oxidative stress response, lipid metabolism/modification, and genomic integrity. Finally, based on bioinformatics analysis, we identified multiple disease-relevant genes in eight well-known ASD/SCZ associated CNV loci (e.g., 22q11.2, 3q29). Our findings suggest an etiological overlap of ASD and SCZ and provide biological insights into these disorders.