Saraiva Leonardo Cardoso, Cappi Carolina, Simpson Helen Blair, Stein Dan J, Viswanath Biju, van den Heuvel Odile A, Reddy Yc Janardhan, Miguel Euripedes C, Shavitt Roseli G
Department & Institute of Psychiatry, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil.
Columbia University Irving Medical Center, Columbia University, New York, NY, 10032, USA.
Fac Rev. 2020 Dec 23;9:30. doi: 10.12703/r/9-30. eCollection 2020.
This article reviews recent advances in the genetics of obsessive-compulsive disorder (OCD). We cover work on the following: genome-wide association studies, whole-exome sequencing studies, copy number variation studies, gene expression, polygenic risk scores, gene-environment interaction, experimental animal systems, human cell models, imaging genetics, pharmacogenetics, and studies of endophenotypes. Findings from this work underscore the notion that the genetic architecture of OCD is highly complex and shared with other neuropsychiatric disorders. Also, the latest evidence points to the participation of gene networks involved in synaptic transmission, neurodevelopment, and the immune and inflammatory systems in this disorder. We conclude by highlighting that further study of the genetic architecture of OCD, a great part of which remains to be elucidated, could benefit the development of diagnostic and therapeutic approaches based on the biological basis of the disorder. Studies to date revealed that OCD is not a simple homogeneous entity, but rather that the underlying biological pathways are variable and heterogenous. We can expect that translation from bench to bedside, through continuous effort and collaborative work, will ultimately transform our understanding of what causes OCD and thus how best to treat it.
本文综述了强迫症（OCD）遗传学的最新进展。我们涵盖了以下方面的研究：全基因组关联研究、全外显子组测序研究、拷贝数变异研究、基因表达、多基因风险评分、基因-环境相互作用、实验动物系统、人类细胞模型、影像遗传学、药物遗传学以及内表型研究。这些研究结果强调了强迫症的遗传结构高度复杂且与其他神经精神疾病有共同之处这一观点。此外，最新证据表明参与突触传递、神经发育以及免疫和炎症系统的基因网络也参与了该疾病。我们在结论中强调，强迫症遗传结构的很大一部分仍有待阐明，对其进一步研究可能有益于基于该疾病生物学基础的诊断和治疗方法的开发。迄今为止的研究表明，强迫症并非一个简单的同质实体，而是其潜在的生物学途径具有变异性和异质性。我们可以期待，通过持续努力和合作，从实验室到临床的转化最终将改变我们对强迫症病因以及最佳治疗方法的理解。
