Gene expression networks regulated by human personality
: del Val Coral, Díaz de la Guardia-Bolívar Elisa, Zwir Igor, Mishra Pashupati P., Mesa Alberto, Salas Ramiro, Poblete Guillermo F., de Erausquin Gabriel, Raitoharju Emma, Kähönen Mika, Raitakari Olli, Keltikangas-Järvinen Liisa, Lehtimäki Terho, Cloninger Claude Robert
Publisher: Springer Nature
: 2024
: Molecular Psychiatry
: Molecular Psychiatry
: 29
: 2241
: 2260
: 1476-5578
DOI: https://doi.org/10.1038/s41380-024-02484-x
: https://www.nature.com/articles/s41380-024-02484-x
: https://research.utu.fi/converis/portal/detail/Publication/387285798
Genome-wide association studies of human personality have been carried out, but transcription of the whole genome has not been studied in relation to personality in humans. We collected genome-wide expression profiles of adults to characterize the regulation of expression and function in genes related to human personality. We devised an innovative multi-omic approach to network analysis to identify the key control elements and interactions in multi-modular networks. We identified sets of transcribed genes that were co-expressed in specific brain regions with genes known to be associated with personality. Then we identified the minimum networks for the co-localized genes using bioinformatic resources. Subjects were 459 adults from the Young Finns Study who completed the Temperament and Character Inventory and provided peripheral blood for genomic and transcriptomic analysis. We identified an extrinsic network of 45 regulatory genes from seed genes in brain regions involved in self-regulation of emotional reactivity to extracellular stimuli (e.g., self-regulation of anxiety) and an intrinsic network of 43 regulatory genes from seed genes in brain regions involved in self-regulation of interpretations of meaning (e.g., production of concepts and language). We discovered that interactions between the two networks were coordinated by a control hub of 3 miRNAs and 3 protein-coding genes shared by both. Interactions of the control hub with proteins and ncRNAs identified more than 100 genes that overlap directly with known personality-related genes and more than another 4000 genes that interact indirectly. We conclude that the six-gene hub is the crux of an integrative network that orchestrates information-transfer throughout a multi-modular system of over 4000 genes enriched in liquid-liquid-phase-separation (LLPS)-related RNAs, diverse transcription factors, and hominid-specific miRNAs and lncRNAs. Gene expression networks associated with human personality regulate neuronal plasticity, epigenesis, and adaptive functioning by the interactions of salience and meaning in self-awareness. © The Author(s) 2024.
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This project was financially supported by grant PID20210125017OB-I00 funded by MCIN/AEI/10.13039/501100011033 and by “ERDF: A way of making Europe”, and the Anthropedia Foundation. Elisa Diaz de la Guardia-Bolivar was funded by a doctoral fellowship, PRE2019-089807, from the Spanish Ministry of Science and Innovation (MCIN/AEI/10.13039/501100011033) and European Social Fund (ESF), “ESF investing in your future”. Ramiro Salas was funded by the Veteran Administration (VHA I01CX001937) and the Menninger Clinic Foundation. The Young Finns Study has been financially supported by the Academy of Finland: grants 356405, 322098, 286284, 134309 (Eye), 126925, 121584, 124282, 255381, 256474, 283115, 319060, 320297, 314389, 338395, 330809, and 104821, 129378 (Salve), 117797 (Gendi), and 141071 (Skidi); the Social Insurance Institution of Finland; Competitive State Research Financing of the Expert Responsibility area of Kuopio, Tampere and Turku University Hospitals (grant X51001); Juho Vainio Foundation; Paavo Nurmi Foundation; Finnish Foundation for Cardiovascular Research ; Finnish Cultural Foundation; The Sigrid Juselius Foundation; Tampere Tuberculosis Foundation; Emil Aaltonen Foundation; Yrjö Jahnsson Foundation; Signe and Ane Gyllenberg Foundation; Diabetes Research Foundation of Finnish Diabetes Association; EU Horizon 2020 (grant 755320 for TAXINOMISIS and grant 848146 for To Aition); European Research Council (grant 742927 for MULTIEPIGEN project); Tampere University Hospital Supporting Foundation, Finnish Society of Clinical Chemistry and the Cancer Foundation Finland. Pashupati P. Mishra was supported by the Academy of Finland (Grant number: 349708) and Emma Raitoharju (grants: 330809, 338395).
