Mental Health Research Center, 34 Kashirskoye shosse, 115522 Moscow, Russia.
Institute of Gene Biology, Russian Academy of Sciences, 34/5 Vavilova Street, 119334 Moscow, Russia.
Cells. 2020 Jan 18;9(1):246. doi: 10.3390/cells9010246.
Recent advances in psychiatric genetics have led to the discovery of dozens of genomic loci associated with schizophrenia. However, a gap exists between the detection of genetic associations and understanding the underlying molecular mechanisms. This review describes the basic approaches used in the so-called post-GWAS studies to generate biological interpretation of the existing population genetic data, including both molecular (creation and analysis of knockout animals, exploration of the transcriptional effects of common variants in human brain cells) and computational (fine-mapping of causal variability, gene set enrichment analysis, partitioned heritability analysis) methods. The results of the crucial studies, in which these approaches were used to uncover the molecular and neurobiological basis of the disease, are also reported.
精神遗传学的最新进展导致了数十个与精神分裂症相关的基因组位点的发现。然而，在检测到遗传关联和理解潜在的分子机制之间存在差距。这篇综述描述了所谓的 GWAS 后研究中用于对现有群体遗传数据进行生物学解释的基本方法，包括分子方法（创建和分析基因敲除动物，探索人类脑细胞中常见变异的转录效应）和计算方法（因果变异性的精细映射、基因集富集分析、遗传分解分析）。还报告了使用这些方法揭示疾病的分子和神经生物学基础的关键研究的结果。
