20.500.12556/RUL-144201 Targeted sequencing approach comprehensive analysis of DNA methylation and gene expression across blood and brain regions in suicide victims Objectives: Epigenetic mechanisms are involved in regulation of many pathologies, including suicidal behaviour. However, the factors through which epigenetics affect suicidal behaviour are not fully understood. Methods: We analysed DNA methylation of eight neuropsychiatric genes (NR3C1, SLC6A4, HTR1A, TPH2, SKA2, MAOA, GABRA1, and NRIP3) in brain regions (hippocampus, insula, amygdala, Brodmann area 46) and blood of 25 male suicide victims and 28 male control subjects, using bisulphite next-generation sequencing. Results: Comparing mean methylation values, notable changes were observed in NR3C1 (insula p-value = 0.05), HTR1A (insula p-value < 0.001, blood p-value = 0.001), SKA2 (insula p-value = 0.03, blood p-value = 0.016), MAOA (blood p-value < 0.001), GABRA1 (insula p-value = 0.05, blood p-value = 0.024) and NRIP3 (hippocampus p-value = 0.001, insula p-value = 0.002, amygdala p-value = 0.014). Comparing methylation pattern between blood and brain, similarity was observed between blood and insula for HTR1A. Gene expression analysis in hippocampus revealed changes in expression of NR3C1 (p-value = 0.049), SLC6A4 (p-value = 0.017) and HTR1A (p-value = 0.053). Conclusions: Results provide an insight into the altered state of DNA methylation in suicidal behaviour. Epigenetic differences could therefore affect suicidal behaviour in both previously known and in novel neuropsychiatric candidate genes. suicidal behaviour epigenetics next-generation sequencing biomarker psychiatry samomorilno vedenje epigenetika sekvenciranje naslednje generacije true false true Angleški jezik Slovenski jezik Članek v reviji 2023-02-03 16:29:30 2023-02-03 16:29:34 2023-02-14 03:34:49 0000-00-00 00:00:00 2022 0 0 Str. 12–23 no. 1 Vol. 24 2022 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616.89 1814-1412 10.1080/15622975.2022.2046291 98996483 Targeted_sequencing_approach_Comprehensive_analysis_o.pdf Targeted_sequencing_approach_Comprehensive_analysis_o.pdf 1 66C3AFA4AAAE79EA70C33670999E4CFD 2399368bdec4ab99fa4b180ce3d9862c1787ea7e0e70e399fa34b7aed53f416b 0d35ab08-ab7e-11ed-9c94-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=166523 https://www.tandfonline.com/doi/full/10.1080/15622975.2022.2046291 0 81fe85e4-a3d7-11ed-9c94-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=166403 Medicinska fakulteta 0 0 0