All for one and one for all: heterogeneity of genetic etiologies in neurodevelopmental psychiatric disorders.

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.

亚历山大·仲马的名言“人人为我，我为人人”概括了我们目前对神经发育性精神障碍（NPD）的基因组结构的理解，比如自闭症谱系障碍、双相情感障碍和精神分裂症。许多具有较大效应量的罕见基因组变异已被确定；它们加在一起可以解释很大一部分NPD。同时，一种罕见的基因组变异可以导致上述所有NPD。最后，个体效应量较小的常见基因组变异可以组合起来进一步解释NPD的风险。我们如何调和解释一种临床诊断的不同基因组变异，以及由一种基因组变异产生的不同临床诊断呢？在这里，我们讨论一个理解NPD中遗传和临床异质性的框架。