Next steps for ptsd genomics: from loci to function
Ended Project Grant Awarded Last action
- Award ID
- R01MH133268
- Recipient
-
The Mclean Hospital Corporation UEI MCKWJYCWNVN3
- Awarding agency
-
National Institute of Mental Health
National Institutes of Health, Department of Health and Human Services
- Obligated
- $4,861,325
Award facts
- Assistance listing
- 93.242 Mental Health Research Grants
- Completion date
- Place of performance
- Belmont, MA 02478, USA
Award details come from USAspending.gov.
Description
- Abstract
- Post-traumatic stress disorder (PTSD) is a severe mental disorder that develops in some victims of trauma but not all. Notably, the mechanisms underlying the development and pathophysiology of PTSD remain unknown, and reliable diagnostic biomarkers, as well as targeted therapeutic interventions, are still lacking. Our research team has employed genome-wide association studies (GWAS) to successfully identify PTSD risk loci as part of the psychiatric genomic consortium for PTSD. We have also used and developed methods to link PTSD risk loci to molecular mechanisms for experimental follow-up. This proposal seeks to fine map the latest, robust PTSD risk loci by linking multi-omic and cell type- specific molecular mechanisms in the amygdala, hippocampus and prefrontal cortex, and specific PTSD-asso- ciated phenotypes. In aim 1, we will identify causal variants and genes in the PTSD risk loci and conduct RNA expression, DNA methylation and protein expression analyses to identify region-specific and across-region gene networks associated with PTSD that involve causal variants and genes. In aim 2, we will identify causal variants and genes in the PTSD risk loci at the brain cell type-specific level and gene molecular alterations across cell types associated with PTSD via single-nucleus (SN) RNA-SEQ- and multiome-SEQ. We validate prioritized variants using in vitro with SNP-sepcific crispr-editing of induced pluripotent stem cells (IPSC) derived neural cultures exposed to glucocorticoids. In aim 3, we will perform a phenomic characterization of the prioritized PTSD vari- ants, genes and networks resulting from aims 1 and 2, explore PTSD subtypes based on implicated phenotypes, and evaluate associated polygenic risk scores to characterize the clinical significance of the fine-mapping AP- proaches. This study will greatly improve our understanding of the brain multi-omic and multi-cell type mechanisms, as well as phenomically characterize the causal risk variants, genes, and networks, and will point toward novel targets for intervention in PTSD.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $0 | |
| Amendment | $836,968 | |
| Amendment | $836,968 | |
| Amendment | $0 | |
| Amendment | $0 | |
| Amendment | $0 | |
| Amendment | $121,693 | |
| Amendment | $689,594 | |
| Amendment | $689,594 | |
| Amendment | $0 | |
| Amendment | $0 | |
| Amendment | $843,254 | |
| Original award | $843,254 |
Show all 13
Subawards
| Subrecipient | Amount | Awarded |
|---|---|---|
| University Of California, San Diego | $118,279 | |
| The Research Foundation For The State University Of New York | $43,212 | |
| University Of California, San Diego | $220,361 | |
| The Research Foundation For The State University Of New York | $79,056 |
Quick answers
Who received award R01MH133268?
R01MH133268 was awarded to The Mclean Hospital Corporation by National Institute of Mental Health (National Institutes of Health) on May 17, 2024.
How much is award R01MH133268 worth?
$4,861,325 has been obligated on R01MH133268.
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