Leukocyte methylomic imprints of exposure to the genocide against the Tutsi in Rwanda: a pilot epigenome-wide analysis

• Published in: Epigenomics Vol. 14; no. 1; pp. 11 - 25
• Main Authors: Musanabaganwa, Clarisse, Wani, Agaz H, Donglasan, Janelle, Fatumo, Segun, Jansen, Stefan, Mutabaruka, Jean, Rutembesa, Eugene, Uwineza, Annette, Hermans, Erno J, Roozendaal, Benno, Wildman, Derek E, Mutesa, Leon, Uddin, Monica
• Format: Journal Article
• Language: English
• Published: England Future Medicine Ltd 01-01-2022
• Subjects: Child; differentially methylated region; DNA Methylation; epigenetics; Epigenome; epigenomic; Female; Genocide; Humans; intergenerational transmission; Leukocytes; maternal stress; methylation; offspring; Pregnancy; Preliminary Communication; PTSD; Rwanda; Stress Disorders, Post-Traumatic; Survivors; trauma; Rwanda; PTSD; offspring; trauma; differentially methylated region; maternal stress; methylation; genocide; epigenomic; epigenetics; intergenerational transmission
• ISSN: 1750-1911; 1750-192X
• DOI: 10.2217/epi-2021-0310

We conducted a pilot epigenome-wide association study of women from Tutsi ethnicity exposed to the genocide while pregnant and their resulting offspring, and a comparison group of women who were pregnant at the time of the genocide but living outside of Rwanda.
Fifty-nine leukocyte-derived DNA samples survived quality control: 33 mothers (20 exposed, 13 unexposed) and 26 offspring (16 exposed, 10 unexposed). Twenty-four significant differentially methylated regions (DMRs) were identified in mothers and 16 in children.
genocide exposure was associated with CpGs in three of the 24 DMRs:
,
 and
, with higher DNA methylation in exposed versus unexposed offspring. Of note,
and
show significant correlation between brain and blood DNA methylation within individuals, suggesting these peripherally derived signals of genocide exposure may have relevance to the brain.
The 1994 Rwandan genocide against ethnic Tutsi has been associated with adverse mental health outcomes in survivors decades later, but the molecular mechanisms that contribute to this association remain poorly characterized. Epigenetic mechanisms such as DNA methylation regulate gene function and change in response to life experiences. We identified differentially methylated regions (DMRs) in genocide-exposed versus unexposed mothers and children.
genocide exposure was linked with methylation differences in three maternal DMRs, with higher methylation in exposed offspring. Two of three DMRs show correlation between brain and blood methylation within individuals, suggesting that peripherally derived signals of genocide exposure may be relevant to the brain.