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Transgenerational Epigenomics of Trauma and PTSD in Rwanda

Award Number: U01MH115485
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/20/2017
PERIOD OF PERFORMANCE END DATE: 06/30/2023

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Transgenerational Epigenomics of Trauma and PTSD in Rwanda - Project Summary The goal of the proposed work is to characterize the transgenerational genomic impact of genocide exposure and post-traumatic stress disorder (PTSD) in women survivors of the Rwandan genocide and their offspring. PTSD is a common and debilitating mental disorder that has a profound public health impact. Between April and June 1994, almost one million people died in the Rwandan genocide against ethnic Tutsi. Twenty years later the long-term impact is illustrated by the prevalence of PTSD in Rwandan adults at 26.1 % and there is strong evidence pointing towards the transgenerational transmission of PTSD. PTSD has a known etiologic component: exposure to an extreme traumatic stressor involving life threat, which induces a biological cascade that includes epigenetic modification of loci whose activity contributes to psychopathological development. In addition, our study in Rwanda showed that transmission of PTSD to the offspring of genocide-exposed mothers was associated with transmission of biological alterations of the hypothalamic-pituitary-adrenal (HPA) axis and epigenetic modifications of the glucocorticoid receptor (NR3C1) gene, a key player in the glucocorticoid receptor regulatory network (GRRN). Building upon these recent findings, the proposed work seeks to characterize the transgenerational epigenetic effects of PTSD and trauma exposure due to the Rwandan genocide. We will employ genome-scale technologies and focus initial analyses on regulation of GRRN and related HPA axis genes, which have been associated with PTSD in recent genome-wide work. Specifically, we will test 100 DNA samples from our existing biobank, previously established in support of our pilot study. We will extend the existing biobank by collecting new specimens from women who were pregnant during the Rwandan genocide and their resulting children, as well their younger siblings, and a demographically matched, non-genocide exposed control group. We will perform additional analyses on a subsample of these specimens both in Rwanda and through the H3Africa network to test additional hypotheses. Our proposal is directly aimed at a key mission of RFA-RM-16-015, to support human genomics research that will not only generate important findings relevant to human health, but also serve as a vehicle to improve the research capacity of African laboratories and scientists at the institutions where the research is carried out. It also directly addresses NIMH strategic objectives 1.2: Identify the genomic and non-genomic factors associated with mental illnesses and 2.1: Characterize the developmental trajectories of brain maturation and dimensions of behavior to understand the roots of mental illnesses across diverse populations. The unique collaboration between the University of Rwanda, the University of Illinois and members of the H3Africa Network will also strengthen the capacity of scientific research through scientific training in Rwanda.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2021	UNIVERSITY OF RWANDA	KK 737 STREET	KIGALI				RWA	Mental Health Research Grants	000	5	12/21/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $258,581 )
2021	2021	UNIVERSITY OF RWANDA	KK 737 STREET, GIKONDO	KIGALI				RWA	Mental Health Research Grants	000	5	8/24/2021	NON-COMPETING CONTINUATION	$258,581
														Subtotal = $258,581

Issue Date FY: 2020 ( Subtotal = $257,614 )
2020	2020	UNIVERSITY OF RWANDA	KK 737 STREET, GIKONDO	KIGALI		4285		RWA	Mental Health Research Grants	000	4	8/24/2020	NON-COMPETING CONTINUATION	$257,614
														Subtotal = $257,614

Issue Date FY: 2019 ( Subtotal = $259,811 )
2019	2019	UNIVERSITY OF RWANDA	KIGALI CENTER	KIGALI		99999		RWA	Mental Health Research Grants	001	3	8/31/2019	NON-COMPETING CONTINUATION	$259,811
2019	2018	UNIVERSITY OF RWANDA	KIGALI CENTER	KIGALI		99999		RWA	Mental Health Research Grants	000	2	7/2/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $259,811

Issue Date FY: 2018 ( Subtotal = $261,769 )
2018	2018	UNIVERSITY OF RWANDA	KIGALI CENTER	KIGALI		99999		RWA	Mental Health Research Grants	000	2	9/11/2018	NON-COMPETING CONTINUATION	$261,769
														Subtotal = $261,769

Issue Date FY: 2017 ( Subtotal = $262,132 )
2017	2017	UNIVERSITY OF RWANDA	GIKONDO	KIGALI				RWA	Mental Health Research Grants	000	1	9/20/2017	NEW	$262,132
														Subtotal = $262,132

Grand Total All Awards = $1,299,907

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Transgenerational Epigenomics of Trauma and PTSD in Rwanda

Award Number: U01MH115485

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/20/2017

PERIOD OF PERFORMANCE END DATE: 06/30/2023

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