CNVs 导致自闭症或精神分裂症的风险会影响对照组的认知能力。
CNVs conferring risk of autism or schizophrenia affect cognition in controls.
机构信息
1] deCODE genetics/Amgen, Sturlugata 8, IS-101 Reykjavík, Iceland [2].
1] Central Institute of Mental Health, University of Heidelberg Medical Faculty Mannheim, 68159 Mannheim, Germany [2].
出版信息
Nature. 2014 Jan 16;505(7483):361-6. doi: 10.1038/nature12818. Epub 2013 Dec 18.
In a small fraction of patients with schizophrenia or autism, alleles of copy-number variants (CNVs) in their genomes are probably the strongest factors contributing to the pathogenesis of the disease. These CNVs may provide an entry point for investigations into the mechanisms of brain function and dysfunction alike. They are not fully penetrant and offer an opportunity to study their effects separate from that of manifest disease. Here we show in an Icelandic sample that a few of the CNVs clearly alter fecundity (measured as the number of children by age 45). Furthermore, we use various tests of cognitive function to demonstrate that control subjects carrying the CNVs perform at a level that is between that of schizophrenia patients and population controls. The CNVs do not all affect the same cognitive domains, hence the cognitive deficits that drive or accompany the pathogenesis vary from one CNV to another. Controls carrying the chromosome 15q11.2 deletion between breakpoints 1 and 2 (15q11.2(BP1-BP2) deletion) have a history of dyslexia and dyscalculia, even after adjusting for IQ in the analysis, and the CNV only confers modest effects on other cognitive traits. The 15q11.2(BP1-BP2) deletion affects brain structure in a pattern consistent with both that observed during first-episode psychosis in schizophrenia and that of structural correlates in dyslexia.
在一小部分精神分裂症或自闭症患者中,其基因组中拷贝数变异 (CNV) 的等位基因可能是导致疾病发病机制的最强因素。这些 CNV 可能为研究大脑功能和功能障碍的机制提供了切入点。它们并非完全显性,为研究其与显性疾病的影响分开提供了机会。在这里,我们在冰岛样本中表明,少数 CNV 明显改变了生育能力(通过 45 岁时的孩子数量来衡量)。此外,我们使用各种认知功能测试来证明携带 CNV 的对照个体的表现水平介于精神分裂症患者和人群对照之间。并非所有的 CNV 都影响相同的认知领域,因此导致或伴随发病机制的认知缺陷因 CNV 而异。携带 15 号染色体 15q11.2 断裂点 1 和 2 之间缺失(15q11.2(BP1-BP2)缺失)的对照个体有阅读障碍和计算障碍的病史,即使在分析中根据智商进行了调整,并且该 CNV 仅对其他认知特征产生适度影响。15q11.2(BP1-BP2)缺失影响大脑结构的模式与精神分裂症首发精神病期间观察到的模式以及阅读障碍中的结构相关性一致。