Ladislav Hosak, Department of Clinical Studies, Faculty of Medicine, University of Ostrava, 708 33 Ostrava, Czech Republic.
World J Psychiatry. 2013 Sep 22;3(3):57-61. doi: 10.5498/wjp.v3.i3.57.
New findings in schizophrenia genetics are based on genome-wide association studies (GWAS), research into DNA copy number variations (CNVs), and endophenotypes. More than 70 genes have recently been suspected to be involved in the genetic background of schizophrenia based on the GWAS´s results. They are typically related to neurodevelopment/neuroplasticity, immunology and neuroendocrinology. Nevertheless, for many detected genes their possible relationship to schizophrenia etiopathogenesis is still unknown. The CNVs at genome loci 1q21.1 (candidate gene e.g., PRKAB2), 2p16.3 (candidate gene e.g., NRXN1), 3q29 (candidate genes e.g., BDH1, DLG1, PAK2 or TFRC), 15q11.2 (candidate gene e.g., CYFIP1), 15q13.3 (candidate gene e.g., CHRNA7), 16p13.1 (candidate genes e.g.,NTAN1 or NDE1) and 22q11.2 (candidate genes e.g., COMT, GSTT2 or PRODH) were associated with schizophrenia most frequently. Genetic research of schizophrenia endophenotypes, usually neurophysiological, neuromotoric, neurocognitive, neuroanatomical, neurological or personality-related, will help us to discover the role of relevant genes in the pathogenesis of schizophrenia. It is also necessary to integrate knowledge from other research platforms in schizophrenia, like epigenetics, studies of gene-environment interactions, transcriptomics, proteomics, metabolomics, neuroimaging and psychopathology. A better knowledge of the genetic background of schizophrenia can lead to changes in the treatment, prevention and genetic counselling. It may also reduce stigma in this severe mental disorder.
精神分裂症遗传学的新发现基于全基因组关联研究(GWAS)、DNA 拷贝数变异(CNVs)研究和内表型。基于 GWAS 的结果,最近有 70 多个基因被怀疑与精神分裂症的遗传背景有关。它们通常与神经发育/神经可塑性、免疫学和神经内分泌学有关。然而,对于许多检测到的基因,它们与精神分裂症病因发病机制的可能关系仍然未知。基因组位点 1q21.1(候选基因如 PRKAB2)、2p16.3(候选基因如 NRXN1)、3q29(候选基因如 BDH1、DLG1、PAK2 或 TFRC)、15q11.2(候选基因如 CYFIP1)、15q13.3(候选基因如 CHRNA7)、16p13.1(候选基因如 NTAN1 或 NDE1)和 22q11.2(候选基因如 COMT、GSTT2 或 PRODH)的 CNVs 与精神分裂症的相关性最高。精神分裂症内表型的遗传研究,通常是神经生理学、神经运动学、神经认知、神经解剖学、神经病学或与人格相关的研究,将帮助我们发现相关基因在精神分裂症发病机制中的作用。还需要整合精神分裂症其他研究平台的知识,如表观遗传学、基因-环境相互作用研究、转录组学、蛋白质组学、代谢组学、神经影像学和精神病理学。更好地了解精神分裂症的遗传背景可以导致治疗、预防和遗传咨询的改变。它还可以减少这种严重精神障碍的污名。