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Use of Next-Gen Sequencing to Identify Genetic Variants that Influence compulsive Oxycodone Intake in Outbred Rats

Award Number: U01DA044451
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Use of Next-Gen Sequencing to Identify Genetic Variants that Influence compulsive Oxycodone Intake in Outbred Rats - Abstract The purpose of the NIDA Animal Genetics Program is to identify genetic, genomic, epigenetic variants, physiology and brain functions that contribute to addiction-like behaviors, related behavioral endophenotypes, and behavioral comorbidities to substance use disorder. During the past four years, our multidisciplinary and highly collaborative consortium has been identifying gene variants that are associated with increased vulnerability to compulsive oxycodone use, tolerance to the analgesic effects of oxycodone, and development of withdrawal-induced hyperalgesia by performing the first GWAS using an advanced model of chronic intravenous oxycodone self-administration in N/NIH heterogeneous stock (HS). We have also created the first preclinical oxycodone biobank which enables researchers who do not have the resources to perform chronic intravenous self-administration or next-generation genome sequencing to perform advanced genetic, molecular, and cellular studies to further our understanding of the biological changes underlying addiction-like behaviors. While these efforts have been very successful in achieving the planned milestones, it has become clear that our project would benefit from an even larger sample size. In particular, increasing sample sizes lead to exponential rather than linear increase in the number of loci identified, and would allow us to identify sex- specific gene variants. Moreover, in the past four years there has been tremendous technological advances in behavioral and genetic analysis that can be leveraged to provide unprecedented access to identify the single nucleotide and structural variants that contribute to complex behavioral endophenotypes of high relevance to oxycodone use-disorders. The first goal of this competing renewal is to double the sample size of the current GWAS to increase the number of gene variants identified including sex-specific variants and meet the demands of the Biobank. The second goal is to use high-throughput behavioral phenotyping using markerless pose estimation based on machine learning with deep neural network to identify behavioral endophenotypes that can help predict and identify individuals with a resistant, mild, moderate, or severe phenotype of oxycodone addiction-like behaviors. The third goal is to use methodological improvements of the genetic analysis, including the analysis of structural variants and tandem repeats, as well as enhanced integration with gene expression data. The fourth goal is to strengthen the oxycodone biobank infrastructure. This project is likely to continue having a sustained and powerful impact on the field because it will provide an exponential increase in the number of genetic loci identified, eQTLs and PheWAS analysis related to addiction-like behavior; establish the first high-throughput behavioral motifs analysis of addiction-like behaviors using parallel video-recording and automated machine learning analysis; identify novel behavioral endophenotypes of vulnerability/resistance to addiction-like behaviors; and expand and improve the Oxycodone Biobank offering and infrastructure.


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 = $839,369 )
2025	2025	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Drug Use and Addiction Research Programs	001	9	3/21/2025	NON-COMPETING CONTINUATION	$839,369
2025	2023	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Drug Use and Addiction Research Programs	000	7	11/14/2024	COMPETING CONTINUATION	$0
														Subtotal = $839,369

Issue Date FY: 2024 ( Subtotal = $1,089,292 )
2024	2024	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Drug Use and Addiction Research Programs	003	8	4/25/2024	NON-COMPETING CONTINUATION	$93,187
2024	2024	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Drug Use and Addiction Research Programs	004	8	8/26/2024	SUPPLEMENT FOR EXPANSION	$157,410
2024	2024	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Drug Use and Addiction Research Programs	000	8	2/23/2024	NON-COMPETING CONTINUATION	$838,695
2024	2023	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Drug Use and Addiction Research Programs	002	7	3/20/2024	COMPETING CONTINUATION	$211,605
2024	2022	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Drug Use and Addiction Research Programs	001	6	3/20/2024	NON-COMPETING CONTINUATION	-$211,605
														Subtotal = $1,089,292

Issue Date FY: 2023 ( Subtotal = $924,074 )
2023	2023	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DRIVE	LA JOLLA	CA	92093	SAN DIEGO	USA	Drug Use and Addiction Research Programs	001	7	5/1/2023	COMPETING CONTINUATION	$924,074
2023	2022	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DRIVE	LA JOLLA	CA	92093	SAN DIEGO	USA	Drug Use and Addiction Research Programs	000	6	4/24/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $924,074

Issue Date FY: 2022 ( Subtotal = $605,080 )
2022	2022	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Drug Use and Addiction Research Programs	000	6	3/3/2022	NON-COMPETING CONTINUATION	$544,570
2022	2022	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Drug Use and Addiction Research Programs	001	6	3/31/2022	NON-COMPETING CONTINUATION	$60,510
														Subtotal = $605,080

Issue Date FY: 2021 ( Subtotal = $622,134 )
2021	2021	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Drug Use and Addiction Research Programs	000	5	2/18/2021	NON-COMPETING CONTINUATION	$622,134
														Subtotal = $622,134

Issue Date FY: 2020 ( Subtotal = $629,605 )
2020	2020	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Drug Use and Addiction Research Programs	002	4	3/6/2020	NON-COMPETING CONTINUATION	$629,605
2020	2019	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Drug Use and Addiction Research Programs	001	3	12/27/2019	SUPPLEMENT FOR EXPANSION	$70,953
2020	2019	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Drug Use and Addiction Research Programs	000	2	12/27/2019	NON-COMPETING CONTINUATION	-$70,953
														Subtotal = $629,605

Issue Date FY: 2019 ( Subtotal = $745,578 )
2019	2019	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR DEPT 621	LA JOLLA	CA	92093	SAN DIEGO	USA	Drug Use and Addiction Research Programs	005	3	9/24/2019	SUPPLEMENT FOR EXPANSION	$0
2019	2019	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR DEPT 621	LA JOLLA	CA	92093	SAN DIEGO	USA	Drug Use and Addiction Research Programs	004	3	9/23/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2019	2019	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR DEPT 621	LA JOLLA	CA	92093	SAN DIEGO	USA	Drug Use and Addiction Research Programs	002	3	9/4/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$600,740
2019	2019	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR DEPT 621	LA JOLLA	CA	92093	SAN DIEGO	USA	Drug Use and Addiction Research Programs	003	3	9/9/2019	SUPPLEMENT FOR EXPANSION	$8,467
2019	2019	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Drug Use and Addiction Research Programs	001	2	9/4/2019	NON-COMPETING CONTINUATION	-$600,740
2019	2019	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Drug Use and Addiction Research Programs	000	2	1/8/2019	NON-COMPETING CONTINUATION	$737,111
														Subtotal = $745,578

Issue Date FY: 2018 ( Subtotal = $794,522 )
2018	2018	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Drug Use and Addiction Research Programs	000	1	2/20/2018	NEW	$794,522
														Subtotal = $794,522

Grand Total All Awards = $6,249,654

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Use of Next-Gen Sequencing to Identify Genetic Variants that Influence compulsive Oxycodone Intake in Outbred Rats

Award Number: U01DA044451

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

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