From the Icahn School of Medicine at Mount Sinai, Departments of Psychiatry, Genetics and Genomic Sciences, New York, NY.
Lieber Institute for Brain Development and the Departments of Psychiatry, Neurology, Neuroscience and Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.
J Clin Psychopharmacol. 2020 Jul/Aug;40(4):323-329. doi: 10.1097/JCP.0000000000001215.
Recent schizophrenia genome-wide association studies (GWAS) have identified genomic variants of common and rare frequency, significantly associated with schizophrenia. While numerous functional genomics efforts are ongoing to elucidate the biological effects of schizophrenia risk variants, a consideration of their therapeutic implications is timely and imperative, for patients as well as for an iterative effect on elucidating the underlying biology and pathophysiology of illness. The current article reviews efforts to translate emerging schizophrenia genomics into novel approaches to target discovery and therapeutic intervention. Though the path from 'genetic risk to therapy' is far from straightforward, there are provocative early possibilities that harbor the promise of treatment based on causation rather than phenomenology, as well as 'precision psychiatry,' a basis for stratifying patients to enable more precise and effective, personalized therapy.
最近的精神分裂症全基因组关联研究（GWAS）已经确定了常见和罕见频率的基因组变异，这些变异与精神分裂症显著相关。虽然目前正在进行大量的功能基因组学研究，以阐明精神分裂症风险变异的生物学效应，但考虑到它们的治疗意义是及时且必要的，这不仅对阐明疾病的潜在生物学和病理生理学有迭代作用，对患者也同样如此。本文综述了将新兴的精神分裂症基因组学转化为靶向发现和治疗干预的新方法的努力。虽然从“遗传风险到治疗”的道路还很漫长，但有一些早期的可能性令人振奋，它们有可能基于病因而不是表型提供治疗，还有“精准精神病学”，这是一种将患者分层的基础，可以实现更精确和有效的个体化治疗。
