Katarina Kouter1, Tomaž Zupanc2, Alja Videtič Paska3. 1. Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, SI-1000 Ljubljana, Slovenia. 2. Institute of Forensic Medicine, Faculty of Medicine, University of Ljubljana, Korytkova ulica 2, SI-1000 Ljubljana, Slovenia. 3. Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, SI-1000 Ljubljana, Slovenia. Electronic address: alja.videtic@mf.uni-lj.si.
Abstract
BACKGROUND: Suicidal behavior is a multifactorial, polygenic state that affects millions worldwide. It is a result of interplay between hereditary and environmental factors, tied together by epigenetics. Despite vast knowledge on suicidality complete mechanism and factors leading to suicide are unknown. However there is an indication between changes in DNA methylation patterns and suicidal behavior. METHODS: To identify differential methylation we formed a homogenous group of male suicide victims who died by hanging and control group. Altogether our study included 18 subjects in which two brain regions, Brodmann area 9 (9 suicide victims and 9 controls)) and hippocampus (6 suicide victims and 6 controls) were investigated using next-generation sequencing (NGS). RESULTS: Our results have shown several differences in methylation level between suicide victims and controls in both brain regions (>25% difference in methylation and q-value < 0.01), with gene ontology pointing towards cell structural integrity and nervous system regulation. Additional gene expression analysis identified changes in two genes, ZNF714 (p-value = 0.002) and NRIP3 (p-value = 0.046). LIMITATIONS: Major limitation is small sample size. Our analysis was conducted on brain tissue including different cell types so the results are a representation of a methylation pattern for the whole brain tissue sample. CONCLUSIONS: We performed a preliminary methylation study with single base pair resolution using NGS on one of the world populations with a very high suicide risk. Obtained results offer novel insights into altered methylation patterns in suicide victims, which could provide a starting point for further studies on clinical samples with highly expressed suicide risk.
BACKGROUND: Suicidal behavior is a multifactorial, polygenic state that affects millions worldwide. It is a result of interplay between hereditary and environmental factors, tied together by epigenetics. Despite vast knowledge on suicidality complete mechanism and factors leading to suicide are unknown. However there is an indication between changes in DNA methylation patterns and suicidal behavior. METHODS: To identify differential methylation we formed a homogenous group of male suicide victims who died by hanging and control group. Altogether our study included 18 subjects in which two brain regions, Brodmann area 9 (9 suicide victims and 9 controls)) and hippocampus (6 suicide victims and 6 controls) were investigated using next-generation sequencing (NGS). RESULTS: Our results have shown several differences in methylation level between suicide victims and controls in both brain regions (>25% difference in methylation and q-value < 0.01), with gene ontology pointing towards cell structural integrity and nervous system regulation. Additional gene expression analysis identified changes in two genes, ZNF714 (p-value = 0.002) and NRIP3 (p-value = 0.046). LIMITATIONS: Major limitation is small sample size. Our analysis was conducted on brain tissue including different cell types so the results are a representation of a methylation pattern for the whole brain tissue sample. CONCLUSIONS: We performed a preliminary methylation study with single base pair resolution using NGS on one of the world populations with a very high suicide risk. Obtained results offer novel insights into altered methylation patterns in suicide victims, which could provide a starting point for further studies on clinical samples with highly expressed suicide risk.
Authors: Ana L Romero-Pimentel; Daniel Almeida; Said Muñoz-Montero; Claudia Rangel; Roberto Mendoza-Morales; Eli E Gonzalez-Saenz; Corina Nagy; Gary Chen; Zahia Aouabed; Jean-Francois Theroux; Gustavo Turecki; Gabriela Martinez-Levy; Consuelo Walss-Bass; Nancy Monroy-Jaramillo; Edith A Fernández-Figueroa; Amalia Gómez-Cotero; Fernando García-Dolores; Mirna E Morales-Marin; Humberto Nicolini Journal: Int J Neuropsychopharmacol Date: 2021-12-08 Impact factor: 5.176