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Integrative analysis of genetic variation and transcription factor networks to elucidate mechanisms of mental health disorders

Award Number: R01MH106842
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2015
PERIOD OF PERFORMANCE END DATE: 10/31/2025

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Integrative analysis of genetic variation and transcription factor networks to elucidate mechanisms of mental health disorders - PROJECT SUMMARY In this project we will bridge the traditionally largely distinct fields of quantitative genetics and mechanistic biology to obtain a mechanistic understanding of regulatory effects of genetic variants in humans. Leveraging on large human data sets providing parallel whole genome and transcriptome sequencing data, we will extend proof-of-principle studies and computational approaches developed and validated in model organisms to achieve improved functional interpretation of GWAS loci associated to mental health disorders. We focus specifically on the role of transcription factors as both upstream regulators of genetic risk variants as well as mediators of downstream network-level effects. As Aim 1, we will develop extend methods to allow accurate modeling of transcription factor activity from transcriptome data from large cohorts of human tissue samples in GTEx, PsychENCODE, and TOPMed cohorts. These data will be used in Aim 2 to dissect the mechanisms underlying proximal genetic regulatory variants in cis. We hypothesize that dynamics of transcription factor activity and binding modifies the effect size of genetic regulatory variants across individuals, tissues, and cell types, and that by modeling this relationship we can detect TFs regulating specific regulatory variants and noncoding disease-associated loci. In parallel Aim 3, we will map network-level trans-acting genetic variants for inter-individual variation in TF activity. Going beyond treating TF activity as a tissue-specific parameter of the cellular environment, we will now consider it as a variable quantitative trait itself, and by GWAS/TWAS for inferred TF activity, we map specific polymorphisms that affect TF activity within each tissue. We anticipate that the trans-acting loci discovered in this analysis will be of major interest not only to basic biology of regulatory networks, but also for explaining GWAS associations to complex diseases, and to mental health in particular.


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 = $776,594 )
2024	2024	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	000	8	10/25/2023	NON-COMPETING CONTINUATION	$698,936
2024	2024	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	001	8	6/27/2024	NON-COMPETING CONTINUATION	$77,658
														Subtotal = $776,594

Issue Date FY: 2023 ( Subtotal = $776,594 )
2023	2023	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	001	7	2/17/2023	NON-COMPETING CONTINUATION	$77,658
2023	2023	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	000	7	11/22/2022	NON-COMPETING CONTINUATION	$698,936
														Subtotal = $776,594

Issue Date FY: 2022 ( Subtotal = $776,594 )
2022	2022	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	001	6	5/12/2022	NON-COMPETING CONTINUATION	$77,658
2022	2022	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	000	6	1/13/2022	NON-COMPETING CONTINUATION	$698,936
														Subtotal = $776,594

Issue Date FY: 2021 ( Subtotal = $776,594 )
2021	2021	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	000	5	10/29/2020	NON-COMPETING CONTINUATION	$698,936
2021	2021	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	002	5	9/10/2021	NON-COMPETING CONTINUATION	$0
2021	2021	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	001	5	4/7/2021	NON-COMPETING CONTINUATION	$77,658
														Subtotal = $776,594

Issue Date FY: 2020 ( Subtotal = $707,826 )
2020	2020	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	000	4	12/9/2019	COMPETING CONTINUATION	$639,638
2020	2020	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	001	4	3/11/2020	COMPETING CONTINUATION	$68,188
														Subtotal = $707,826

Issue Date FY: 2019 ( Subtotal = $0 )
2019	2017	NEW YORK GENOME CENTER, INC.	101 AVE OF THE AMERICAS	NEW YORK	NY	10013	NEW YORK	USA	Mental Health Research Grants	000	3	7/8/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2017 ( Subtotal = $454,356 )
2017	2017	NEW YORK GENOME CENTER, INC.	101 AVE OF THE AMERICAS	NEW YORK	NY	10013	NEW YORK	USA	Mental Health Research Grants	001	3	7/25/2017	NON-COMPETING CONTINUATION	$45,437
2017	2017	NEW YORK GENOME CENTER, INC.	101 AVE OF THE AMERICAS	NEW YORK	NY	10013	NEW YORK	USA	Mental Health Research Grants	000	3	2/8/2017	NON-COMPETING CONTINUATION	$408,919
														Subtotal = $454,356

Issue Date FY: 2016 ( Subtotal = $454,509 )
2016	2016	NEW YORK GENOME CENTER INC	101 AVENUE OF THE AMERICAS	NEW YORK	NY	10013	NEW YORK	USA	Mental Health Research Grants	000	2	2/15/2016	NON-COMPETING CONTINUATION	$454,509
														Subtotal = $454,509

Issue Date FY: 2015 ( Subtotal = $288,628 )
2015	2015	NEW YORK GENOME CENTER INC	101 AVENUE OF THE AMERICAS	NEW YORK	NY	10013	NEW YORK	USA	Mental Health Research Grants	000	1	3/23/2015	NEW	$288,628
														Subtotal = $288,628

Grand Total All Awards = $5,011,695

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Integrative analysis of genetic variation and transcription factor networks to elucidate mechanisms of mental health disorders

Award Number: R01MH106842

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/01/2015

PERIOD OF PERFORMANCE END DATE: 10/31/2025

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