A neurogenetic model for the study of schizophrenia spectrum disorders: the International 22q11.2 Deletion Syndrome Brain Behavior Consortium
A neurogenetic model for the study of schizophrenia spectrum disorders: the International 22q11.2 Deletion Syndrome Brain Behavior Consortium
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DOI：
10.1038/mp.2017.161
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发表时间：
2017-12-01
影响因子：
11
通讯作者：
Morrow, B.
中科院分区：
文献类型：
--
作者：
Gur, R. E.;Bassett, A. S.;Morrow, B.
罕见的拷贝数变异会显着增加精神分裂症的风险，其中 22q11.2 位点始终受到影响。与一般人群相比，患有 22q11.2 缺失综合征 (22q11DS) 的个体患精神分裂症谱系障碍的风险估计增加 25 倍。国际 22q11DS 大脑行为联盟正在从表型和基因组角度研究这种信息丰富的神经遗传综合征。在这里，我们详细介绍了表征与 22q11DS 相关的神经精神和神经行为表型的过程，重点关注精神分裂症和精神病的阈下表达。基因组方法包括全基因组测序和全基因组微阵列技术的结合，可以研究影响精神分裂症相关表型表达的所有可能的 DNA 变异和基因途径。表型丰富的数据集提供了一个前所未有的规模（n = 1616）的精神病学特征样本，该样本揭示了 22q11DS 的神经行为发育过程。这组表型和基因组数据的组合将使假设检验能够阐明精神分裂症谱系疾病发病机制的机制。
Rare copy number variants contribute significantly to the risk for schizophrenia, with the 22q11.2 locus consistently implicated. Individuals with the 22q11.2 deletion syndrome (22q11DS) have an estimated 25-fold increased risk for schizophrenia spectrum disorders, compared to individuals in the general population. The International 22q11DS Brain Behavior Consortium is examining this highly informative neurogenetic syndrome phenotypically and genomically. Here we detail the procedures of the effort to characterize the neuropsychiatric and neurobehavioral phenotypes associated with 22q11DS, focusing on schizophrenia and subthreshold expression of psychosis. The genomic approach includes a combination of whole-genome sequencing and genome-wide microarray technologies, allowing the investigation of all possible DNA variation and gene pathways influencing the schizophrenia-relevant phenotypic expression. A phenotypically rich data set provides a psychiatrically well-characterized sample of unprecedented size (n = 1616) that informs the neurobehavioral developmental course of 22q11DS. This combined set of phenotypic and genomic data will enable hypothesis testing to elucidate the mechanisms underlying the pathogenesis of schizophrenia spectrum disorders.