Opera Medica et Physiologica

The Influence of Genes, miRNAs and Retroelements on Psychological Well-Being

Abstract: 

The heritability of human psychological well-being ranges from 36 to 48%. GWAS conducted between 2016 and 2019 identified 364 SNPs significant for well-being. A significant association with psychological well-being has been shown for the APOE, OXTR, OXT, NMUR2, CNR1, CRHR1, and CYP19A1 genes. The greatest influence on psychological well-being is exerted by allelic variants of the MAYA, 5-HTT, СOMT genes, and the CTRA gene group (conservative transcriptional response to adversity). Brain functioning is influenced by the peculiarities of VNTR distribution in the regulatory regions of the 5-HTT, SLC6A3, AVPR1A, FUS, OXT, PARK7, POMC, TACR3, TRPV1 and TRPV3 genes. These features are due to the individual distribution of SVA (SINE-VNTR-Alu) retroelements, which belong to transposons that are drivers of epigenetic regulation. Features of activation of retroelements located in the regulatory regions of genes may affect the individual level of well-being. This is evidenced by the association with psychological well-being of DRD4, MAOA, SLC6A3, 5-HTT genes alleles, determined by the length of VNTR in their regulatory regions. Evidence of retroelements role in well-being regulation is that retroelements are sources of protein-coding genes and microRNAs involved in brain functioning. The Arc gene, derived from retroelements, is characterized by transport into neuronal dendrites with translation regulation. We analyzed the MDTE DB database on transposon-derived microRNAs and scientific literature. According to the results, 12 miRNAs, derived from transposons, are associated with major depressive disorder. The data obtained indicate the influence of transposons on psychological well-being, which is assessed by the absence of depression.