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Using the Genetic Architecture of Substance Use Disorders to Advance Gene Identification and Understanding of Pathways of Risk

Award Number: R01DA050721
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Using the Genetic Architecture of Substance Use Disorders to Advance Gene Identification and Understanding of Pathways of Risk - Project Summary This project has two complementary goals: (1) to advance discovery of genes involved in substance use disorders using new multivariate genomic techniques, and (2) to characterize the risk associated with identified variants in diverse longitudinal samples in order to understand the spectrum of phenotypes associated with identified variants, across development, and in conjunction with the environment. Each of these areas represents critical steps in using genetic data to improve prevention, intervention, and treatment for substance use disorders (SUDs), and will lay the foundation as we move into an era of personalized medicine. Human gene identification efforts for substance use disorders lag behind other areas of psychiatry, in part due to constrained sample sizes of available SUD cases. However, recent meta-analyses of substance-related phenotypes such as age of initiation, consumption and problems, reveal significant genetic correlations across substance use outcomes, as well as with numerous other psychiatric and behavioral traits. These findings map onto twin data demonstrating significant genetic correlations across substance use disorders and other externalizing traits. This project will (Aim 1) apply new multivariate genetic methods to capitalize on genetic sharing between substance use phenotypes and related traits in order to boost power to detect common variants associated with substance use outcomes, and to characterize the latent pathways by which genetic variants operate. Bioinformatic characterization of these identified genetic variants will provide insight into underlying biological risk pathways, and phenotypic characterization of resultant polygenic risk scores will help us understand how risk unfolds across development and in conjunction with the environment. We will apply results from the multivariate analyses to two complementary longitudinal datasets, consisting of a population-based and high-risk sample, in order to (Aim 2a) map the behavioral phenotypes associated with the genetic risk scores identified in Aim 1 across adolescence and emerging adulthood; (Aim 2b) test for pathways of risk specific to sex and racial/ethnic background; and (Aim 2c) test for moderation of genetic risk by key environmental factors. Jointly, these analyses will advance our understanding of how genetic variation contributes to risk for substance use 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: 2024 ( Subtotal = $690,317 )
2024	2024	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	65 BERGEN ST	NEWARK	NJ	07107	ESSEX	USA	Drug Use and Addiction Research Programs	002	5	5/9/2024	NON-COMPETING CONTINUATION	$690,317
2024	2023	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	65 BERGEN ST	NEWARK	NJ	07107	ESSEX	USA	Drug Use and Addiction Research Programs	001	4	2/26/2024	SUPPLEMENT FOR EXPANSION	$0
2024	2023	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	65 BERGEN ST	NEWARK	NJ	07107	ESSEX	USA	Drug Use and Addiction Research Programs	000	4	11/1/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $690,317

Issue Date FY: 2023 ( Subtotal = $768,203 )
2023	2023	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	65 BERGEN ST	NEWARK	NJ	07107	ESSEX	USA	Drug Use and Addiction Research Programs	003	4	6/26/2023	NON-COMPETING CONTINUATION	$0
2023	2023	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	65 BERGEN ST	NEWARK	NJ	07107	ESSEX	USA	Drug Use and Addiction Research Programs	004	4	6/26/2023	SUPPLEMENT FOR EXPANSION	$240,813
2023	2023	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	65 BERGEN ST	NEWARK	NJ	07107	ESSEX	USA	Drug Use and Addiction Research Programs	000	4	4/21/2023	NON-COMPETING CONTINUATION	$527,390
2023	2022	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	65 BERGEN ST	NEWARK	NJ	07107	ESSEX	USA	Drug Use and Addiction Research Programs	002	3	5/25/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$329,291
2023	2021	VIRGINIA COMMONWEALTH UNIVERSITY	910 WEST FRANKLIN ST	RICHMOND	VA	23284	RICHMOND CITY	USA	Drug Use and Addiction Research Programs	001	2	5/25/2023	NON-COMPETING CONTINUATION	-$329,291
														Subtotal = $768,203

Issue Date FY: 2022 ( Subtotal = $570,140 )
2022	2022	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	65 BERGEN ST	NEWARK	NJ	07107	ESSEX	USA	Drug Use and Addiction Research Programs	001	3	8/9/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$570,140
2022	2021	VIRGINIA COMMONWEALTH UNIVERSITY	912 W FRANKLIN ST	RICHMOND	VA	23284	RICHMOND CITY	USA	Drug Use and Addiction Research Programs	000	2	8/9/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $570,140

Issue Date FY: 2021 ( Subtotal = $554,862 )
2021	2021	VIRGINIA COMMONWEALTH UNIVERSITY	912 W FRANKLIN ST	RICHMOND	VA	23284	RICHMOND CITY	USA	Drug Use and Addiction Research Programs	000	2	4/15/2021	NON-COMPETING CONTINUATION	$554,862
														Subtotal = $554,862

Issue Date FY: 2020 ( Subtotal = $588,712 )
2020	2020	VIRGINIA COMMONWEALTH UNIVERSITY	912 W FRANKLIN ST	RICHMOND	VA	23284	RICHMOND CITY	USA	Drug Use and Addiction Research Programs	000	1	6/24/2020	NEW	$588,712
														Subtotal = $588,712

Grand Total All Awards = $3,172,234

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Using the Genetic Architecture of Substance Use Disorders to Advance Gene Identification and Understanding of Pathways of Risk

Award Number: R01DA050721

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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