In 1994, one of the most horrific civil wars took place in the rural country of Rwanda. In a period of about 100 days, nearly one million people died. Most of the dead were Tutsi – a minority group that was targeted for extermination by the then government. In the aftermath of the genocide, many survivors were left with mental health problems such as posttraumatic stress disorder (PTSD) and depression.

Although decades have passed, the Rwandan people continue to cope with their enduring anguish – not only among those who lived through it but also by a second generation. This observation suggests that trauma, if not healed, can be passed on to descendants. Yet, how this occurs on a molecular level is poorly understood.

Now, new research from the University of South Florida (USF) and Center for Global Health and Infectious Disease Research is helping to provide insight into the mental health issues that have emerged from the Tutsi ethnic group genocide. Published in the January 2022 issue of Epigenomics, this study is a first-of-its-kind to examine the epigenomes of Tutsi women who were pregnant during the 1994 attacks and their children versus non-exposed pregnant Tutsi women and their offspring.

The human genome is the complete assembly of a person’s DNA that makes them unique. On the other hand, the epigenome is the myriad of chemical compounds that attach to the DNA, directing the genes as to which proteins to make for particular cells. The genome is always the same in every cell, but the epigenome differs and can be modified. In addition, the epigenetic chemical tags or “marks” can be altered by the environment, and sometimes, these marks get passed on to future generations.

One notable epigenetic mark that is stable and inheritable is DNA methylation. This mechanism regulates gene function and can change in response to life experiences. For example, previous articles have discussed how DNA methylation can be altered in patients with PTSD and that stress-related epigenetic changes can be passed down to babies born to mothers under extreme stress.

Here, the researchers’ epigenome-wide study found that the genocide-exposed mothers and children had significantly differentially methylated regions (DMRs) compared to unexposed mothers and children. And, several of these methylation differences occurred in genes that are known to be associated with a risk for certain mental disorders like PTSD and depression.

“These [epigenetic modifications] can happen in a shorter time frame than is needed for changes to the underlying DNA sequence of genes. Our study found that prenatal genocide exposure was associated with an epigenetic pattern suggestive of reduced gene function in offspring,” said Monica Uddin, author, and professor in USF’s College of Public Health.

The team compiled their results using DNA extracted from the blood of 59 participants, half of which were exposed personally or in utero to the genocide. Exposure included individuals that were impacted by trauma, such as evading capture or rape, witnessing a serious attack or murder, and seeing dead and mutilated bodies.

The data showed in utero genocide exposure was associated with methylation differences in 3 maternal DMRs: BCOR, PRDM8, and VWDE, with higher DNA methylation in exposed offspring. The data also showed that these individuals had a correlation between brain and blood methylation for BCOR and VWDE, indicating that peripherally obtained signals of genocide exposure may be of importance to brain function.

As part of the Human, Heredity & Health in Africa (H3Africa) consortium, this study supports other early life (in-utero) development studies and provides valuable data that can help improve both African and worldwide health.

“The Rwandan people who are in this study and community as a whole really want to know what happened to them,” said author Derek Wildman, USF professor. “Because there’s a lot of PTSD and other mental health disorders in Rwanda and people want answers as to why they’re experiencing these feelings and having these issues.”

Nearly 28 years later, the children of the exposed pregnant mothers are having children of their own. The researchers noted that they will soon start to look at how the genocide trauma affected the third generation, specifically evaluating their potential risk for mental health disorders.

Source: C. Musanabaganwa et al. (2022). Leukocyte methylomic imprints of exposure to the genocide against the Tutsi in Rwanda: a pilot epigenome-wide analysis. Epigenomics.

Reference: Study finds Rwandan genocide chemically modified the DNA of victims and victims’ offspring. University of South Florida (USF Innovation), January 10, 2022.

This curated information was sourced from the www.whatisepigenetics.com page.