Li Ming, Yue Weihua
Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, China.
CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China.
Mol Neuropsychiatry. 2018 Dec;4(3):119-133. doi: 10.1159/000493941. Epub 2018 Nov 7.
Recent large-scale genetic approaches, such as genome-wide association studies, have identified multiple genetic variations that contribute to the risk of mental illnesses, among which single nucleotide polymorphisms (SNPs) within or near the vaccinia related kinase 2 () gene have gained consistent support for their correlations with multiple psychiatric and neurological disorders including schizophrenia (SCZ), major depressive disorder (MDD), and genetic generalized epilepsy. For instance, the genetic variant rs1518395 in showed genome-wide significant associations with SCZ (35,476 cases and 46,839 controls, = 3.43 × 10) and MDD (130,620 cases and 347,620 controls, = 4.32 × 10) in European populations. This SNP was also genome-wide significantly associated with SCZ in Han Chinese population (12,083 cases and 24,097 controls, = 3.78 × 10), and all associations were in the same direction of allelic effects. These studies highlight the potential roles of in the central nervous system, and this gene therefore might be a good candidate to investigate the shared genetic and molecular basis between SCZ and MDD, as it is one of the few genes known to show genome-wide significant associations with both illnesses. Furthermore, the gene was found to be involved in multiple other congenital deficits related to the malfunction of neurodevelopment, adding further support for the involvement of this gene in the pathogenesis of these neurological and psychiatric illnesses. While the precise function of in these conditions remains unclear, preliminary evidence suggests that it may affect neuronal proliferation and migration via interacting with multiple essential signaling pathways involving other susceptibility genes/proteins for psychiatric disorders. Here, we have reviewed the recent progress of genetic and molecular studies of , with an emphasis on its role in psychiatric illnesses and neurological functions. We believe that attention to this important gene is necessary, and further investigations of may provide hints into the underlying mechanisms of SCZ and MDD.
最近的大规模遗传学方法，如全基因组关联研究，已经确定了多种导致精神疾病风险的基因变异，其中痘苗相关激酶2（VRK2）基因内部或附近的单核苷酸多态性（SNP）与包括精神分裂症（SCZ）、重度抑郁症（MDD）和遗传性全身性癫痫在内的多种精神和神经疾病的相关性获得了一致支持。例如，VRK2基因中的遗传变异rs1518395在欧洲人群中与精神分裂症（35476例病例和46839例对照，P = 3.43×10⁻⁹）和重度抑郁症（130620例病例和347620例对照，P = 4.32×10⁻¹⁰）呈现全基因组显著关联。该SNP在汉族人群的精神分裂症患者中（12083例病例和24097例对照，P = 3.78×10⁻⁸）也呈现全基因组显著关联，并且所有关联的等位基因效应方向相同。这些研究突出了VRK2在中枢神经系统中的潜在作用，因此该基因可能是研究精神分裂症和重度抑郁症之间共享遗传和分子基础的良好候选基因，因为它是已知的少数几个与这两种疾病都呈现全基因组显著关联的基因之一。此外，发现VRK2基因还参与了多个与神经发育功能障碍相关的其他先天性缺陷，这进一步支持了该基因参与这些神经和精神疾病发病机制的观点。虽然VRK2在这些情况下的确切功能仍不清楚，但初步证据表明，它可能通过与涉及其他精神疾病易感基因/蛋白质的多个重要信号通路相互作用来影响神经元的增殖和迁移。在此，我们综述了VRK2基因的遗传和分子研究的最新进展，重点关注其在精神疾病和神经功能中的作用。我们认为关注这个重要基因是必要的，对VRK2的进一步研究可能为精神分裂症和重度抑郁症的潜在机制提供线索。
