Department of Biosciences, Simon Fraser University, Burnaby, BC, V5A 1 S6, Canada.
J Neurodev Disord. 2012 May 30;4(1):15. doi: 10.1186/1866-1955-4-15.
Autism spectrum disorders and schizophrenia have been associated with an overlapping set of copy number variant loci, but the nature and degree of overlap in copy number variants (deletions compared to duplications) between these two disorders remains unclear.
We systematically evaluated three lines of evidence: (1) the statistical bases for associations of autism spectrum disorders and schizophrenia with a set of the primary CNVs thus far investigated, from previous studies; (2) data from case series studies on the occurrence of these CNVs in autism spectrum disorders, especially among children, and (3) data on the extent to which the CNVs were associated with intellectual disability and developmental, speech, or language delays. We also conducted new analyses of existing data on these CNVs in autism by pooling data from seven case control studies.
Four of the CNVs considered, dup 1q21.1, dup 15q11-q13, del 16p11.2, and dup 22q11.21, showed clear statistical evidence as autism risk factors, whereas eight CNVs, del 1q21.1, del 3q29, del 15q11.2, del 15q13.3, dup 16p11.2, dup 16p13.1, del 17p12, and del 22q11.21, were strongly statistically supported as risk factors for schizophrenia. Three of the CNVs, dup 1q21.1, dup 16p11.2, and dup 16p13.1, exhibited statistical support as risk factors for both autism and schizophrenia, although for each of these CNVs statistical significance was nominal for tests involving one of the two disorders. For the CNVs that were statistically associated with schizophrenia but were not statistically associated with autism, a notable number of children with the CNVs have been diagnosed with autism or ASD; children with these CNVs also demonstrate a high incidence of intellectual disability and developmental, speech, or language delays.
These findings suggest that although CNV loci notably overlap between autism and schizophrenia, the degree of strongly statistically supported overlap in specific CNVs at these loci remains limited. These analyses also suggest that relatively severe premorbidity to CNV-associated schizophrenia in children may sometimes be diagnosed as autism spectrum disorder.
自闭症谱系障碍和精神分裂症与一组重叠的拷贝数变异（CNV）位点相关，但这两种疾病之间的 CNV（缺失与重复相比）的性质和重叠程度尚不清楚。
我们系统地评估了三条证据线：（1）从先前的研究中，评估自闭症谱系障碍和精神分裂症与迄今为止研究的一组主要 CNV 相关的统计基础；（2）自闭症谱系障碍中发生这些 CNV 的病例系列研究数据，特别是在儿童中；（3）这些 CNV 与智力残疾以及发育、言语或语言延迟相关的程度的数据。我们还通过汇集来自七个病例对照研究的数据，对这些 CNV 在自闭症中的现有数据进行了新的分析。
考虑的四个 CNV，dup1q21.1、dup15q11-q13、del16p11.2 和 dup22q11.21，作为自闭症风险因素有明确的统计证据，而八个 CNV，del1q21.1、del3q29、del15q11.2、del15q13.3、dup16p11.2、dup16p13.1、del17p12 和 del22q11.21，作为精神分裂症的风险因素有很强的统计支持。三个 CNV，dup1q21.1、dup16p11.2 和 dup16p13.1，作为自闭症和精神分裂症的风险因素都有统计学支持，尽管对于这些 CNV 中的每一个，对于涉及两种疾病之一的测试，统计学意义都是名义上的。对于与精神分裂症统计学相关但与自闭症统计学无关的 CNV，许多携带这些 CNV 的儿童被诊断为自闭症或 ASD；这些 CNV 的儿童也表现出智力残疾以及发育、言语或语言延迟的高发率。
这些发现表明，尽管自闭症和精神分裂症之间的 CNV 位点明显重叠，但这些位点特定 CNV 的强烈统计学支持重叠程度仍然有限。这些分析还表明，儿童与 CNV 相关的精神分裂症的相对严重的前期症状有时可能被诊断为自闭症谱系障碍。
