Rare genomic disorders (RGDs) confer elevated risk for neurodevelopmental psychiatric disorders. In this era of intense genomics discoveries, the landscape of RGDs is rapidly evolving. However, there has not been comparable progress to date in scalable, harmonized phenotyping methods. As a result, beyond associations with categorical diagnoses, the effects on dimensional traits remain unclear for many RGDs. The nature and specificity of RGD effects on cognitive and behavioral traits is an area of intense investigation: RGDs are frequently associated with more than one psychiatric condition, and those studied to date affect, to varying degrees, a broad range of developmental and cognitive functions. Although many RGDs have large effects, phenotypic expression is typically influenced by additional genomic and environmental factors. There is emerging evidence that using polygenic risk scores in individuals with RGDs offers opportunities to refine prediction, thus allowing for the identification of those at greatest risk of psychiatric illness. However, translation into the clinic is hindered by roadblocks, which include limited genetic testing in clinical psychiatry, and the lack of guidelines for following individuals with RGDs, who are at high risk of developing psychiatric symptoms. The Genes to Mental Health Network (G2MH) is a newly funded National Institute of Mental Health initiative that will collect, share, and analyze large-scale data sets combining genomics and dimensional measures of psychopathology spanning diverse populations and geography. The authors present here the most recent understanding of the effects of RGDs on dimensional behavioral traits and risk for psychiatric conditions and discuss strategies that will be pursued within the G2MH network, as well as how expected results can be translated into clinical practice to improve patient outcomes.

罕见基因组疾病（RGD）会导致神经发育精神疾病的风险升高。在这个基因组学发现不断涌现的时代，RGD 的前景正在迅速发展。然而，迄今为止，在可扩展、统一的表型分析方法方面还没有取得可比的进展。因此，除了与分类诊断的关联之外，对于许多 RGD 来说，对维度特征的影响仍不清楚。 RGD 对认知和行为特征影响的性质和特异性是一个深入研究的领域：RGD 通常与不止一种精神疾病相关，迄今为止的研究在不同程度上影响了广泛的发育和认知功能。尽管许多 RGD 具有很大的影响，但表型表达通常受到其他基因组和环境因素的影响。越来越多的证据表明，对 RGD 患者使用多基因风险评分提供了完善预测的机会，从而可以识别出那些患精神疾病的风险最大的人。然而，向临床的转化受到障碍的阻碍，其中包括临床精神病学中的基因检测有限，以及缺乏跟踪 RGD 患者的指南，这些患者出现精神症状的风险很高。基因到心理健康网络 (G2MH) 是国家心理健康研究所新资助的一项计划，将收集、共享和分析大规模数据集，结合基因组学和跨不同人群和地理的精神病理学维度测量。 作者在此介绍了 RGD 对维度行为特征和精神疾病风险影响的最新理解，并讨论了 G2MH 网络中将采取的策略，以及如何将预期结果转化为临床实践，以改善患者的治疗结果。