Wednesday, October 1, 2025 10/1/2025

Genetic and social determinants of pharmacological health outcomes in ancestrally diverse populations

Award Number: R01HG012824
ORGANIZATION: NATIONAL HUMAN GENOME RESEARCH INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2023
PERIOD OF PERFORMANCE END DATE: 04/30/2028

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Genetic and social determinants of pharmacological health outcomes in ancestrally diverse populations - PROJECT SUMMARY/ABSTRACT Pharmacogenomics has the potential to dramatically improve health care outcomes, but is currently failing on diversity among its research participants. As a consequence, we do not fully understand all of the factors influencing pharmacogical response in underrepresented populations, including those that contribute to racial/ethnic differences in drug efficacy and safety as reported by Food and Drug Administration (FDA) drug labels. For example, the clinical validity of genetic variants that are common in research participants from historically-excluded populations (e.g., lower proportions of European genetic ancestry), but rare in wellrepresented study populations remains unknown. In addition, gene expression studies have already provided insight into the underlying biology of disease susceptibility for numerous conditions beyond what genome wide association study (GWAS) results alone have discovered, but have not been fully applied to studies of pharmacogenomic discovery. Furthermore, social determinants of health may impact pharmacological drug response from a biological standpoint even after taking into account the effects of these factors on drug adherence, access, and utilization (e.g. social determinants of epigenetics). Addressing this gap in knowledge has the potential to prevent future healthcare disparities that may be exacerbated as the infrastructure to support clinical pharmacogenomics continues to gain traction across health institutions nationwide. Furthermore, elucidation of the genetic and nongenetic contributors to differences in drug response across race/ethnicity will obviate the use of this population descriptor as a proxy for these factors. Pharmacogenomic studies using large, diverse datasets are necessary to ensure that advances in this field benefit individuals equitably. Our primary goal in this project is to identify genetic and social determinants of pharmacological drug response among racial/ethnic minorities. To accomplish this goal, we will leverage data from the Kaiser Permanente Research Biobank (KPRB) and the National Institutes of Health (NIH) All Of Us research program, which are two of the largest electronic health record-linked biobanks in the United States. These cohorts are ideal for the proposed studies because they are large (>400,000 participants each), diverse (>25% racial/ethnic minorities), linked to genome-wide genetic data, and capture social determinants of health. In Aim 1, we will evaluate the relative contribution of genetic ancestry versus social factors on race/ethnicity- based differences in drug efficacy and safety. In Aim 2, we will identify genome-wide polymorphisms predictive of drug effects in historically-excluded populations from large pharmacogenetics studies. In Aim 3, we will use ancestry-specific gene expression results to identify genetic determinants of drug response. The aims will be carried out by an established multidisciplinary team of experts in clinical pharmacology, cardiovascular epidemiology, and molecular genetics. These findings from the current study will help to inform clinical decisions impacting communities historically-excluded from biomedical research.


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 = $559,265 )
2025	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Human Genome Research	008	3	9/18/2025	SUPPLEMENT FOR EXPANSION	$32,650
2025	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Human Genome Research	007	3	9/16/2025	NON-COMPETING CONTINUATION	$526,615
2025	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Human Genome Research	002	2	4/11/2025	SUPPLEMENT FOR EXPANSION	$0
2025	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Human Genome Research	005	2	7/11/2025	SUPPLEMENT FOR EXPANSION	$0
2025	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Trans-NIH Research Support	000	2	4/11/2025	NON-COMPETING CONTINUATION	$0
2025	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Human Genome Research	004	2	7/11/2025	SUPPLEMENT FOR EXPANSION	$0
2025	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Trans-NIH Research Support	006	2	9/16/2025	NON-COMPETING CONTINUATION	$0
2025	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Trans-NIH Research Support	003	2	7/11/2025	NON-COMPETING CONTINUATION	$0
2025	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Human Genome Research	001	2	4/11/2025	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $559,265

Issue Date FY: 2024 ( Subtotal = $670,397 )
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Trans-NIH Research Support	000	2	4/30/2024	NON-COMPETING CONTINUATION	$526,647
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Human Genome Research	001	2	9/14/2024	SUPPLEMENT FOR EXPANSION	$71,210
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Human Genome Research	002	2	9/18/2024	SUPPLEMENT FOR EXPANSION	$72,540
														Subtotal = $670,397

Issue Date FY: 2023 ( Subtotal = $616,738 )
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Trans-NIH Research Support	000	1	6/26/2023	NEW	$616,738
														Subtotal = $616,738

Grand Total All Awards = $1,846,400

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Genetic and social determinants of pharmacological health outcomes in ancestrally diverse populations

Award Number: R01HG012824

ORGANIZATION: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/01/2023

PERIOD OF PERFORMANCE END DATE: 04/30/2028

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