Vorstman Jacob, Sebat Jonathan, Bourque Vincent-Raphaël, Jacquemont Sébastien
Department of Psychiatry, The Hospital for Sick Children, Toronto, ON, Canada.
Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
Mol Psychiatry. 2025 Jan;30(1):229-236. doi: 10.1038/s41380-024-02706-2. Epub 2024 Aug 30.
The role of genetic testing in the domain of neurodevelopmental and psychiatric disorders (NPDs) is gradually changing from providing etiological explanation for the presence of NPD phenotypes to also identifying young individuals at high risk of developing NPDs before their clinical manifestation. In clinical practice, the latter implies a shift towards the availability of individual genetic information predicting a certain liability to develop an NPD (e.g., autism, intellectual disability, psychosis etc.). The shift from mostly a posteriori explanation to increasingly a priori risk prediction is the by-product of the systematic implementation of whole exome or genome sequencing as part of routine diagnostic work-ups during the neonatal and prenatal periods. This rapid uptake of genetic testing early in development has far-reaching consequences for psychiatry: Whereas until recently individuals would come to medical attention because of signs of abnormal developmental and/or behavioral symptoms, increasingly, individuals are presented based on genetic liability for NPD outcomes before NPD symptoms emerge. This novel clinical scenario, while challenging, also creates opportunities for research on prevention interventions and precision medicine approaches. Here, we review why optimization of individual risk prediction is a key prerequisite for precision medicine in the sphere of NPDs, as well as the technological and statistical methods required to achieve this ambition.
基因检测在神经发育和精神疾病（NPDs）领域的作用正在逐渐转变，从为NPD表型的存在提供病因学解释，转变为在临床症状出现之前识别出有患NPDs高风险的年轻人。在临床实践中，后者意味着向提供预测患某种NPD（如自闭症、智力障碍、精神病等）易感性的个体基因信息转变。从主要是事后解释到越来越多的事前风险预测的转变，是在新生儿期和产前阶段将全外显子组或基因组测序作为常规诊断检查的一部分进行系统实施的副产品。在发育早期迅速采用基因检测对精神病学产生了深远影响：直到最近，个体因发育异常和/或行为症状的迹象而引起医学关注，而现在，越来越多的个体是在NPD症状出现之前，基于患NPD结果的基因易感性前来就诊。这种新的临床情况虽然具有挑战性，但也为预防干预和精准医学方法的研究创造了机会。在此，我们回顾为什么优化个体风险预测是NPDs领域精准医学的关键前提，以及实现这一目标所需的技术和统计方法。
