Abstract

Modern biological models based on stress-diathesis consider suicide an independent form of behavior, which is the basis for the search for specific genetic markers. The current review embraces all presently existing GWAS studies of suicidal phenotypes (suicidal ideation, attempts, and completed suicides). Fifteen studies based on this strategy and using different approaches to data analysis, including comparisons with existing databases on psychiatric genetics, pathway analysis, protein-protein interactions, functional grouping of genes, and enrichment analysis are discussed. In contrast to the candidate gene studies which intensively discussed associations with neurotransmitter systems of the brain (indol- and catecholamines, GABA, excitatory aminoacids, etc.), GWAS suggest a rather different set of factors. Many findings are among the genes involved in neurodevelopment, neuroplasticity, cell adhesion and migration, proliferation, and intracellular signaling, as well as immune system functioning. We consider that this confirms the relevance of the stress-vulnerability models implying a key role of the early development, which affects neuroplasticity. Stress as a systemic reaction of the organism demonstrates a significant role in the genesis of suicidal behavior. It should be noted that findings of different studies rarely coincide, thus demonstrating heterogeneous findings. This may be due to differences in bioinformatics approaches, description of phenotypes, and design of the study. Future accumulation of data especially considering the ethnic factor, increase in the sample size, and meta-analyses may clarify the polygenic nature of suicidal behavior and identify genetic markers that are valuable for both understanding the pathogenesis of suicidality and suicide prediction and prevention.

中文翻译：

---

自杀学的全基因组关联研究：近期成就回顾

摘要

基于应激素质的现代生物学模型认为自杀是一种独立的行为形式，这是寻找特定遗传标记的基础。当前的评价涵盖了所有现有的关于自杀表型的GWAS研究（自杀意念，尝试和完全自杀）。讨论了基于此策略并使用不同方法进行数据分析的15项研究，包括与现有的精神病学遗传学数据库比较，途径分析，蛋白质-蛋白质相互作用，基因功能分组和富集分析。与大量讨论与大脑神经递质系统（吲哚和儿茶酚胺，GABA，兴奋性氨基酸等）的关联的候选基因研究相反，GWAS提出了一组完全不同的因素。许多发现都与神经发育，神经可塑性，细胞粘附和迁移，增殖，细胞内信号转导以及免疫系统功能有关。我们认为，这证实了压力-脆弱性模型的相关性，暗示了早期发展的关键作用，这影响了神经可塑性。压力作为生物体的系统性反应，在自杀行为的发生中起着重要作用。应该注意的是，不同研究的发现很少重合，因此表明了异类发现。这可能是由于生物信息学方法，表型描述和研究设计的差异所致。未来的数据积累，尤其是考虑种族因素，样本量增加，