Alexandre Dumas' famous phrase All for One and One for All recapitulates our current understanding of the genomic architecture of neurodevelopmental psychiatric disorders (NPD), like autism Spectrum disorder, bipolar disorder, and schizophrenia. Many rare genomic variants of large effect size have been identified; all of them together can explain a significant proportion of NPD. In parallel, one rare genomic variant can cause all of the above NPD. Finally, common genomic variants of individually small effect size can be combined to further explain risk for NPD. How do we reconcile different genomic variants accounting for one clinical diagnosis, and different clinical diagnoses arising from a single genomic variant? Here, we discuss a framework to understand genetic and clinical heterogeneity in NPD.

中文翻译：

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一劳永逸：神经发育性精神疾病中遗传病因的异质性。

亚历山大·杜马斯（Alexandre Dumas）著名的短语“一劳永逸”和“一劳永逸”概括了我们目前对神经发育性精神疾病（NPD）的基因组结构的理解，例如自闭症谱系障碍，双相情感障碍和精神分裂症。已经鉴定出许多影响大小很大的稀有基因组变异体。所有这些都可以解释NPD的很大一部分。同时，一种罕见的基因组变异会导致上述所有NPD。最后，可以将单个效应量较小的常见基因组变体组合起来，以进一步解释NPD的风险。我们如何调和用于一项临床诊断的不同基因组变异，以及由单一基因组变异引起的不同临床诊断？在这里，我们讨论一个框架，以了解NPD中的遗传和临床异质性。