Targeted sequencing approach : comprehensive analysis of DNA methylation and gene expression across blood and brain regions in suicide victims

Kouter, Katarina (author), Zupanc, Tomaž (author), Videtič Paska, Alja (author)

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.

• Language: English
• Keywords: suicidal behaviour, epigenetics, next-generation sequencing, biomarker, psychiatry
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2022
• Number of pages: Str. 12–23
• Numbering: Vol. 24, no. 1
• PID: 20.500.12556/RUL-144201
• UDC: 616.89
• ISSN on article: 1814-1412
• DOI: 10.1080/15622975.2022.2046291
• COBISS.SI-ID: 98996483
• Publication date in RUL: 03.02.2023

Record is a part of a journal

• Title: The world journal of biological psychiatry
• Publisher: WFSBP, Taylor & Francis
• ISSN: 1814-1412
• COBISS.SI-ID: 521963801

Licences

• License: CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
• Link: http://creativecommons.org/licenses/by-nc-nd/4.0/
• Description: The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.

Secondary language

• Language: Slovenian
• Keywords: samomorilno vedenje, epigenetika, sekvenciranje naslednje generacije