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Assessing Clinical Utility of Polygenic Risk Scores in Ancestrally Diverse Real-World Cohorts

Award Number: F99HG013437
ORGANIZATION: NATIONAL HUMAN GENOME RESEARCH INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 01/01/2024
PERIOD OF PERFORMANCE END DATE: 03/31/2025

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Assessing Clinical Utility of Polygenic Risk Scores in Ancestrally Diverse Real-World Cohorts - Project Summary The long-term goal of this project is to assess the utility of trans-ancestry polygenic risk scores (PRSs) in real-world, ancestrally diverse cohorts to predict health outcomes in clinical settings. PRSs represent a numerical summary of an individuals’ genetic risk for a trait or disease based on combined effects of genetic variants across the human genome. A PRS has many potential benefits such as efficient disease screening/prediction and therapeutic prevention/intervention and may be useful in saving many lives and resources. However, the application of PRS for risk prediction in clinical settings alongside non-genetic risk factors such as lifestyle and environmental risk factors remains largely unknown, especially in underrepresented populations, yet may be of added benefit. A better understanding of PRS utility for clinical risk prediction, and limitations of PRS in diverse, real-world populations is needed to realize the potential benefits of the applications of PRS across all populations. This proposal encompasses a training and research plan to develop the candidate’s expertise in genetic epidemiology research. The specific aims are to 1a) Investigate the association of trans-ancestry blood pressure (BP) PRS with hypertension incidence and progression in individuals across their life course, 1b) Investigate the association of trans-ancestry BP PRS with incidence of BP-related health outcomes including stroke, cardiovascular disease (CVD), dementia, kidney disease, heart failure and all-cause mortality in ancestrally diverse individuals (F99 dissertation research); and 2) Assess clinical utility of trans-ancestry prostate cancer PRS for predicting prostate cancer incidence and aggressiveness, incorporating prostate serum antigen (PSA) level trajectories and other clinical risk factors (K00 postdoctoral direction). This proposed project will generate new knowledge and provide training for the candidate’s advancement to become an independent investigator focused on genetic epidemiology of complex polygenic diseases and traits in ancestrally diverse populations. The research is relevant to NHGRI’s bold predictions by 2030, number 6 “The regular use of genomic information will have transitioned from boutique to mainstream in all clinical settings, making genomic testing as routine as complete blood counts” and number 9: “Individuals from ancestrally diverse backgrounds will benefit equitably from advances in human genomics.”


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 = $21,811 )
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	002	2	4/23/2025	NON-COMPETING CONTINUATION	-$23,543
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	001	2	1/20/2025	NON-COMPETING CONTINUATION	$44,074
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	000	1	1/16/2025	NEW	$1,280
														Subtotal = $21,811

Issue Date FY: 2024 ( Subtotal = $42,794 )
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Human Genome Research	002	1	1/22/2024	NEW	$0
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Human Genome Research	001	1	1/18/2024	NEW	$0
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Human Genome Research	003	1	1/31/2024	NEW	$0
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Human Genome Research	000	1	12/20/2023	NEW	$42,794
														Subtotal = $42,794

Grand Total All Awards = $64,605

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Assessing Clinical Utility of Polygenic Risk Scores in Ancestrally Diverse Real-World Cohorts

Award Number: F99HG013437

ORGANIZATION: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 01/01/2024

PERIOD OF PERFORMANCE END DATE: 03/31/2025

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