Thursday, November 21, 2024 11/21/2024

Leveraging genetic and electronic health record data to identify novel targets and drugs for treating alcohol use disorder

Award Number: R01AA030041
ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PROJECT SUMMARY/ABSTRACT While four medications for treating alcohol use disorder (AUD) are approved by the Food and Drug Administration (FDA), many patients do not benefit from them. Moreover, while genome-wide association studies (GWASs) of alcohol consumption and problematic alcohol use (PAU; i.e., a phenotype that combines AUD diagnoses and a measure of harmful drinking) have yielded many significant single nucleotide polymorphisms (SNPs) that affect risk, these have yielded few drug targets for treating AUD. Hence, there is an unmet need to identify drug targets for the development of novel and/or repurposed drugs to treat AUD. Recent research indicates that targeting disease mechanisms with genetic support can increase the success rate in drug development and that modules (i.e., biological networks surrounding disease-associated genes) are enriched for targets of approved drugs. Thus, genes affecting alcohol consumption and risk of PAU and their associated modules could yield new targets and drugs for therapeutic repurposing. Furthermore, the availability of large electronic health records (EHR) datasets makes it possible to explore whether exposure to FDA-approved drugs can lead to improvements in medical conditions other than the ones for which they are approved, such as AUD, and potentially be repurposed. This proposal will build upon prior work by the study team and leverage advances in genomics and access to the Veterans Affairs (VA) EHR through the VA Informatics and Computing Infrastructure (VINCI) to: 1) elucidate modules linked to alcohol consumption and PAU (Aims 1 and 3); and 2) identify promising drugs for repurposing to treat AUD (Aim 2). The general hypotheses for Aims 1-2 are: 1) the genes implicated in the identified modules will be targeted by numerous approved drugs; and 2) of the drugs with sufficient patient data in the VA EHR, there will be evidence that they reduce alcohol consumption in propensity score analyses. The hypothesis for Aim 3 is that the analysis will identify top ranked modules that are enriched for biological processes with relevance to alcohol consumption and PAU. In sum, this proposal combines psychiatric genetic and pharmacoepidemiologic methods to identify novel targets and evaluate promising drugs to be repurposed for treating AUD. An atheoretical, genetic data-driven approach to selecting promising FDA-approved drugs and then testing them in the EHR using propensity score methods has not previously been done in psychiatry, including for AUD. This project is made possible by recent advances in GWAS of alcohol consumption and PAU, drug target linking, and the cultivation of EHRs for genetic and other analyses. This approach to drug prioritization could uncover unique drugs to be tested in follow-up clinical trials and novel targets to be evaluated in preclinical studies.


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 = $544,668 )
2024	2024	THE HENRY M. JACKSON FOUNDATION FOR THE ADVANCEMENT OF MILITARY MEDICINE, INC.	6720A ROCKLEDGE DR	BETHESDA	MD	20817	MONTGOMERY	USA	Alcohol Research Programs	000	3	6/10/2024	NON-COMPETING CONTINUATION	$553,007
2024	2024	THE HENRY M. JACKSON FOUNDATION FOR THE ADVANCEMENT OF MILITARY MEDICINE, INC.	6720A ROCKLEDGE DR	BETHESDA	MD	20817	MONTGOMERY	USA	Alcohol Research Programs	002	3	7/12/2024	NON-COMPETING CONTINUATION	-$8,339
2024	2023	THE HENRY M. JACKSON FOUNDATION FOR THE ADVANCEMENT OF MILITARY MEDICINE, INC.	6720A ROCKLEDGE DR	BETHESDA	MD	20817	MONTGOMERY	USA	Alcohol Research Programs	001	2	6/12/2024	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $544,668

Issue Date FY: 2023 ( Subtotal = $646,598 )
2023	2023	THE HENRY M. JACKSON FOUNDATION FOR THE ADVANCEMENT OF MILITARY MEDICINE, INC.	6720A ROCKLEDGE DR	BETHESDA	MD	20817	MONTGOMERY	USA	Alcohol Research Programs	000	2	5/31/2023	NON-COMPETING CONTINUATION	$545,977
2023	2023	THE HENRY M. JACKSON FOUNDATION FOR THE ADVANCEMENT OF MILITARY MEDICINE, INC.	6720A ROCKLEDGE DR	BETHESDA	MD	20817	MONTGOMERY	USA	Alcohol Research Programs	001	2	9/12/2023	SUPPLEMENT FOR EXPANSION	$100,621
														Subtotal = $646,598

Issue Date FY: 2022 ( Subtotal = $553,341 )
2022	2022	HENRY M. JACKSON FOUNDATION FOR THE ADVANCEMENT OF MILITARY MEDICINE, INC., THE	6720-A ROCKLEDGE DR STE 100	BETHESDA	MD	20817	MONTGOMERY	USA	Alcohol Research Programs	000	1	5/26/2022	NEW	$553,341
														Subtotal = $553,341

Grand Total All Awards = $1,744,607

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Leveraging genetic and electronic health record data to identify novel targets and drugs for treating alcohol use disorder

Award Number: R01AA030041

ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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