DNA methylation and exposure to violence among African American young adult males

Forough Saadatmand; Katherine Gurdziel; Latifa Jackson; Bernard Kwabi-Addo; Douglas M Ruden

doi:10.1016/j.bbih.2021.100247

DNA methylation and exposure to violence among African American young adult males

Brain Behav Immun Health. 2021 Mar 29:14:100247. doi: 10.1016/j.bbih.2021.100247. eCollection 2021 Jul.

Authors

Forough Saadatmand¹, Katherine Gurdziel², Latifa Jackson^{1

3}, Bernard Kwabi-Addo⁴, Douglas M Ruden^{5

6}

Affiliations

¹ Department of Pediatrics, College of Medicine, Howard University, Washington, DC, USA.
² Office of the Vice President of Research, Wayne State University, Detroit, MI, USA.
³ W. Montague Cobb Research Laboratory, College of Arts and Sciences, Howard University, Washington, DC, USA.
⁴ Department of Biochemistry and Molecular Biology, College of Medicine, Howard University, Washington, DC, USA.
⁵ Department of Ob/Gyn, CS Mott Center for Human Growth and Development, Wayne State University School of Medicine, Detroit, MI, USA.
⁶ Institutes for Environmental Health Science, Wayne State University School of Medicine, Detroit, MI, USA.

Abstract

Exposure to violence (ETV) has been linked to epigenomics mechanisms such as DNA methylation (DNAm). We used epigenetic profiling of blood collected from 32 African American young adult males who lived in Washington DC to determine if changes in DNAm at CpG sites affiliated with nervous and immune system were associated with exposure to violence. Pathway analysis of differentially methylated regions comparing high and low ETV groups revealed an enrichment of gene sets annotated to nervous system and immune ontologies. Many of these genes are known to interact with each other which suggests DNAm alters gene function in the nervous and immune system in response to ETV. Using data from a unique age group, young African American adult males, we provide evidence that lifetime ETV could impact DNA methylation in genes impacted at Central Nervous System and Immune Function sites.

Method: Methylation analysis was performed on DNA collected from the blood of participants classified with either high or low lifetime ETV. Illumina®MethylationEPIC Beadchips (~850k CpG sites) were processed on the iScan System to examine whole-genome methylation differences. Differentially methylated CpG-sites between high (n = 19) and low (n = 13) groups were identified using linear regression with violence and substance abuse as model covariates. Gene ontology analysis was used to identify enrichment categories from probes annotated to the nearest gene.

Results: A total of 595 probes (279 hypermethylated; 316 hypomethylated) annotated to 383 genes were considered differentially methylated in association with ETV. Males with high ETV showed elevated methylation in several signaling pathways but were most impacted at Central Nervous System and Immune Function affiliated sites. Eight candidate genes were identified that play important biological roles in stress response to violence with HDAC4 (10%), NR4A3 (11%), NR4A2 (12%), DSCAML1(12%), and ELAVL3 (13%) exhibiting higher levels in the low ETV group and DLGAP1 (10%), SHANK2 (10%), and NRG1(11%) having increased methylation in the high ETV group. These findings suggest that individuals subjected to high ETV may be at risk for poor health outcomes that have not been reported previously.

Keywords: African americans; DNA methylation; Epigenetic; Exposure to violence; Young adults.

Abstract

Grants and funding