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Integrative approaches to identification and interpretation of genes underlying psychiatric disorders

Award Number: R01MH121394
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/10/2020
PERIOD OF PERFORMANCE END DATE: 05/31/2025

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Integrative approaches to identification and interpretation of genes underlying psychiatric disorders - Psychiatric disorders contribute substantially to the disease burden in the United States and worldwide. There is strong evidence for a genetic contribution to many psychiatric illnesses. In recent years, with the advancement of high throughput genomic technologies and the availability of large samples, remarkable success has been made in risk gene discovery for major psychiatric disorders [e.g., schizophrenia (SCZ), bipolar disorder (BD) and major depressive disorder (MDD)] through genome-wide association studies (GWAS). However, due to the high complexity of the human genome, few causal genes or variants have been identified within GWAS risk loci, thus, to date, limiting the potential of translating these genetic findings into biological mechanisms. There is now a great need to pinpoint causal genes/variants at the known GWAS risk loci and to understand their causal mechanisms, as well as to discover novel genes from novel risk loci. There is also growing evidence that risk variants from GWAS tend to be located in regulatory DNA regions in disease-relevant tissues or cell types, suggesting that risk variants may act through regulation of gene expression. Studies leveraging diverse functional genomic resources may benefit psychiatric risk gene discovery and result in better prediction of their biological relevance. This proposal aims to employ highly integrative approaches to identify causal genes and regulatory noncoding variants underlying SCZ, BD, and MDD. Our specific aims are: 1) Integrate GWAS with brain methylome for risk gene discovery, by leveraging a dense high-resolution reference panel of DNAm from whole genome bisulfite sequencing of DNA from three different brain regions (frontal cortex, hippocampus, and caudate) and an enlarged array-based reference panel; 2) Apply a deep learning approach to predicting disease-relevant regulatory variants, by employing features from disease-relevant gene regulatory networks and functional genomic annotations within brain tissues and neural cell types; and 3) Map prioritized genes and variants to specific brain cell types and brain function. We have assembled an outstanding multidisciplinary team with expertise in psychiatric genetics, bioinformatics, machine learning, and neuroimaging. Our goal is to apply multidisciplinary and cutting-edge analytical strategies to help address the challenges arising in the post-GWAS era. The identification and characterization of risk genes and noncoding regulatory variants would help improve our understanding of the biological mechanisms that underlie psychiatric illnesses, moving us closer to designing effective prevention and treatment for these disorders.


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: 2025 ( Subtotal = $0 )
2025	2023	THE LIEBER INSTITUTE	855 N WOLFE ST STE 300	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Mental Health Research Grants	000	4	6/18/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $595,673 )
2023	2023	LIEBER INSTITUTE, INC.	855 N WOLFE ST STE 300	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Mental Health Research Grants	000	4	5/25/2023	NON-COMPETING CONTINUATION	$595,673
														Subtotal = $595,673

Issue Date FY: 2022 ( Subtotal = $595,673 )
2022	2022	LIEBER INSTITUTE, INC.	855 N WOLFE ST STE 300	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Mental Health Research Grants	000	3	5/27/2022	NON-COMPETING CONTINUATION	$595,673
														Subtotal = $595,673

Issue Date FY: 2021 ( Subtotal = $595,673 )
2021	2021	LIEBER INSTITUTE, INC.	855 N WOLFE ST STE 300	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Mental Health Research Grants	000	2	5/27/2021	NON-COMPETING CONTINUATION	$595,673
														Subtotal = $595,673

Issue Date FY: 2020 ( Subtotal = $647,274 )
2020	2020	LIEBER INSTITUTE, INC.	855 N WOLFE ST	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Mental Health Research Grants	000	1	8/10/2020	NEW	$647,274
														Subtotal = $647,274

Grand Total All Awards = $2,434,293

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Integrative approaches to identification and interpretation of genes underlying psychiatric disorders

Award Number: R01MH121394

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/10/2020

PERIOD OF PERFORMANCE END DATE: 05/31/2025

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