Analysis of Aggressive Behavior in Young Russian Males Using 250 SNP Markers

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 (TM) 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,LAMC2andITGA2; 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.