Abstract

Until not so long ago, the main area of genetic studies of aggressive behavior was represented by associative analysis of candidate genes, which were identified according to the relationship of phenotypic manifestations of aggression with the functioning of neuromediator and reproductive systems. Recent years have been marked by development of a new direction of genome-wide associative studies of aggression, which makes it possible to detect new genes that previously were not the object of interest to specialists. The present study is an analysis of aggressive behavior in Russian males living in the Moscow metropolis, using a panel of 250 SNP marker loci. In addition to SNP markers of known candidate genes, the panel contained single base substitutions in genes involved in the development and functioning of the brain, in the processes of neuronal development and synaptic plasticity, and in the formation of interneuronal connections, as well as in genes associated with various brain pathologies. The panel of SNP markers also included control genes that were in no way associated with aggressive behavior or behavior in general. These are primarily housekeeping genes, as well as genes encoding proteins associated with chromatid cohesion, etc. Aggressive behavior was self-assessed using the Bass–Perry and reactive–proactive aggression questionnaires. After applying a number of filters, 35 males were included in the final sample. Fragments containing 250 single-nucleotide polymorphic sites of interest were sequenced on the Ion PGM System using the Ion 318™ Chip. The principal component analysis and clustering based on the Bayesian a posteriori probability did not identify subdivisions in the analyzed sample of Russian males. For each aggression scale, a statistically significant association with a specific set of SNP markers was obtained, and only one polymorphic locus rs1047788 was associated with both physical and reactive aggression. Bioinformatic analysis revealed that most of the identified markers are associated with neuropeptides involved in the development and functioning of the nervous system as a whole and its regeneration and in the development of sections of the brain responsible for stress reactions, regulation of the humoral system, and intercellular signaling. For a number of markers from this set, it was possible to identify possible mechanisms of relationship to behavioral traits. The list of identified genes is as follows: corticotropin-releasing hormone, CRH; semenogelin-1 protein, SEMG1; intercellular interaction proteins, LAMC2 and ITGA2; DNA repair endonuclease, ERCC5; cohesin complex protein that provides conjugation of sister chromosomes, ESCO1; transmembrane serine protease, TMPRSS15; apoptosis inhibitor, BIRC5; interferon beta-1, IFNB1; scaffold protein, XRCC1; heat shock protein, HSP90AA1.

中文翻译：

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使用250个SNP标记分析俄罗斯年轻男性的攻击行为

摘要

直到不久之前，攻击性行为的遗传研究的主要领域还包括候选基因的关联分析，这些候选基因是根据攻击的表型表现与神经介质和生殖系统的功能之间的关系而确定的。近年来，以侵略性全基因组关联研究的新方向的发展为标志，这使得有可能检测以前不是专家感兴趣的新基因。本研究使用一组250个SNP标记基因座，分析了居住在莫斯科都会区的俄罗斯男性的攻击行为。除了已知候选基因的SNP标记外，该小组还包含与大脑发育和功能相关的基因中的单碱基取代，在神经元发展和突触可塑性的过程中，在神经元间连接的形成中，以及在与各种脑部疾病相关的基因中。SNP标记物组还包括与侵略行为或一般行为无关的对照基因。这些主要是管家基因，以及编码与染色单体凝聚力相关的蛋白质的基因。使用Bass-Perry和反应性-主动式攻击问卷对攻击行为进行自我评估。在使用许多过滤器后，最终样本中包括35个雄性。使用Ion 318™芯片在Ion PGM系统上对包含250个感兴趣的单核苷酸多态性位点的片段进行测序。基于贝叶斯后验概率的主成分分析和聚类未能在分析的俄罗斯男性样本中识别细分。对于每个攻击规模，均获得了与一组特定SNP标记的统计学显着关联，并且只有一个多态位点rs1047788与物理和反应性攻击相关。生物信息学分析表明，大多数鉴定出的标志物都与神经肽有关，这些神经肽参与整个神经系统的发育和功能及其再生，并参与负责应激反应，调节体液系统和细胞间信号传导。对于该组中的许多标记，有可能确定与行为特征相关的可能机制。CRH ; semenogelin-1蛋白，SEMG1；细胞间相互作用蛋白，LAMC2和ITGA2；DNA修复核酸内切酶ERCC5；黏着蛋白复合蛋白，可提供姐妹染色体ESCO1的结合；跨膜丝氨酸蛋白酶TMPRSS15；凋亡抑制剂，BIRC5；干扰素beta-1，IFNB1；支架蛋白XRCC1 ; 热休克蛋白，HSP90AA1。