A functional SNP in MIR124-1, a brain expressed miRNA gene, is associated with aggressiveness in a Colombian sample

Abstract

Background: Interpersonal violence and suicide are among the main causes of mortality and morbidity around the world. In several developing countries, such as Colombia, they are among the first five entities of public health concern. Aggressiveness is an important endophenotype for aggression and suicidal behavior, having a heritability of around 50%. Exploration of classical candidate genes, involved in serotoninergic and dopaminergic neurotransmission, has identified few consistent risk factors for aggressiveness. miRNAs are a novel class of molecules with a growing role in normal neural function and neuropsychiatric disorders; of special interest, miR-124 is a brain-specific miRNA that is key for neuronal plasticity. We evaluated the hypothesis that a functional polymorphism in MIR124-1 gene might be associated with aggressiveness in a Colombian sample.

Methods: The Spanish adaptation of the refined version of the Aggression Questionnaire and the abbreviated Barratt Impulsiveness Scale were applied to 170 young subjects. The functional SNP in MIR124-1 (rs531564) was genotyped by a TaqMan assay.

Results: We found a significant association between the MIR124-1 and aggressiveness in our sample, with G/G carriers having lower scores (P=0.01). This association seemed to be specific for aggressiveness, as it was not significant for impulsiveness.

Conclusions: We showed for the first time the association of a functional polymorphism in MIR124-1 and aggressiveness. Known targets of miR-124 (such as BDNF and DRD4 genes) could explain the effect of this miRNA on behavior. A future analysis of additional novel functional polymorphisms in other brain expressed miRNAs could be useful for a deeper understanding of aggression in humans.

Keywords: Aggression; Endophenotypes; Latin America; Psychiatric genetics; Violence; ncRNAs.