Genomic Psychiatry Consultation Service, Verrecchia Clinic for Children with Autism and Developmental Disabilities, Bradley Hospital, Providence, RI, United States; Division of Child and Adolescent Psychiatry, Department of Psychiatry and Human Behavior, Warren Alpert Medical School of Brown University, Providence, RI, United States.
Autism & Developmental Medicine Institute, Geisinger, Danville, PA, United States; Genomic Medicine Institute, Geisinger, Danville, PA, United States.
Curr Opin Genet Dev. 2021 Jun;68:71-78. doi: 10.1016/j.gde.2021.02.015. Epub 2021 Mar 25.
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.
大仲马的名言“一人为大家，大家为一人”概括了我们目前对神经发育性精神障碍（NPD），如自闭症谱系障碍、双相情感障碍和精神分裂症的基因组结构的理解。已经确定了许多具有大效应量的罕见基因组变异；它们加在一起可以解释 NPD 的很大一部分。与此同时，一个罕见的基因组变异可以导致所有上述 NPD。最后，个体小效应量的常见基因组变异可以组合在一起，以进一步解释 NPD 的风险。我们如何协调一个临床诊断所涉及的不同基因组变异，以及一个基因组变异所产生的不同临床诊断？在这里，我们讨论了一个理解 NPD 中遗传和临床异质性的框架。
