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Identification of Epigenetics Correlates between Brain and Peripheral Tissues

Award Number: R01MH119165
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/11/2021
PERIOD OF PERFORMANCE END DATE: 11/30/2025

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Identification of Epigenetics Correlates between Brain and Peripheral Tissues - Abstract Psychiatric disorders such as major depressive disorder (MDD) are complex diseases where negative stressors increase the likelihood of its onset through epigenetic changes, such as DNA methylation (DNAm). Presently, disease-associated DNAm patterns of MDD have not been fully elucidated. This is in part due to the reliance of peripheral tissues such as blood, buccal cells, and saliva where it is unknown how DNAm changes from these tissues might be an accurate reflection of those changes in the brain. As such, there is an urgent need to provide a comprehensive database that would cross-compare DNAm patterns between the brain and other peripheral tissues to highlight candidate regions where disease-associated DNAm can be observed. To this end, our overall goal is to establish a comprehensive epigenomic database where DNAm patterns can be cross-compared between key brain regions (e.g., the hippocampus, amygdala, and dorsolateral prefrontal cortex), their neurons and glia components, and peripheral tissues. Our central hypothesis is that disease- associated DNAm will more likely reside in regions that vary in DNAm between different tissues. Our specific aims will address the following questions: In Aim 1, DNAm will be evaluated at a genome-wide level and cross- compared between brain and peripheral tissues to identify regions which have varying DNAm between tissues. In Aim 2, we will expand DNAm assessment in neuron and glia to the aforementioned key brain regions involved in MDD and compare that with peripheral tissues. In Aim 3, disease-associated DNAm regions will be evaluated using pathology-archived brain tissues from 206 MDD cases and 206 matched controls. This is the largest post-mortem study of MDD that specifically evaluates DNAm. Disease-associated DNAm will be overlaid with tissue-specific DNAm to determine regions where MDD-associated DNAm patterns will likely to occur. This proposed study is significant as it will provide a comprehensive epigenetic database that will guide researchers to candidate regions and suitable peripheral tissues to investigate DNAm changes in MDD. Its use may also be extended to other psychiatric disorders. This proposed study is innovative as it uses fresh brain, neuron, glia and peripheral tissues from the same individual to establish an epigenome database. It also uses disease-associated DNAm identified from a large cohort of post-mortem MDD brains to identify regions that are “hot-spots” for disease-associated methylation changes.


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 = $586,547 )
2024	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Mental Health Research Grants	001	6	8/14/2024	NON-COMPETING CONTINUATION	$58,653
2024	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Mental Health Research Grants	000	6	11/22/2023	NON-COMPETING CONTINUATION	$527,894
														Subtotal = $586,547

Issue Date FY: 2023 ( Subtotal = $594,468 )
2023	2023	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Mental Health Research Grants	000	5	11/29/2022	NON-COMPETING CONTINUATION	$535,022
2023	2023	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Mental Health Research Grants	001	5	2/4/2023	NON-COMPETING CONTINUATION	$59,446
														Subtotal = $594,468

Issue Date FY: 2022 ( Subtotal = $594,359 )
2022	2022	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Mental Health Research Grants	004	4	2/22/2022	NON-COMPETING CONTINUATION	$25,793
2022	2022	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Mental Health Research Grants	001	4	1/15/2022	NON-COMPETING CONTINUATION	$534,923
2022	2022	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Mental Health Research Grants	007	4	5/23/2022	NON-COMPETING CONTINUATION	$59,436
2022	2022	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Mental Health Research Grants	005	4	2/23/2022	NON-COMPETING CONTINUATION	-$20,681
2022	2021	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Mental Health Research Grants	000	3	10/26/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2022	2021	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Mental Health Research Grants	003	2	2/18/2022	NON-COMPETING CONTINUATION	-$5,112
2022	2021	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Mental Health Research Grants	006	3	2/23/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$20,681
2022	2020	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Mental Health Research Grants	002	1	2/18/2022	NEW	-$20,681
														Subtotal = $594,359

Issue Date FY: 2021 ( Subtotal = $557,597 )
2021	2021	UNIVERSITY OF IOWA, THE	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Mental Health Research Grants	000	2	1/25/2021	NON-COMPETING CONTINUATION	$615,112
2021	2021	UNIVERSITY OF IOWA, THE	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Mental Health Research Grants	001	2	9/7/2021	NON-COMPETING CONTINUATION	-$610,000
2021	2021	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Mental Health Research Grants	002	3	9/8/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$552,485
														Subtotal = $557,597

Issue Date FY: 2020 ( Subtotal = $631,423 )
2020	2020	UNIVERSITY OF IOWA, THE	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Mental Health Research Grants	000	1	12/16/2019	NEW	$631,423
														Subtotal = $631,423

Grand Total All Awards = $2,964,394

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Identification of Epigenetics Correlates between Brain and Peripheral Tissues

Award Number: R01MH119165

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 06/11/2021

PERIOD OF PERFORMANCE END DATE: 11/30/2025

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