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Advancing the clinical actionability of polygenic scores for coronary artery disease

Award Number: K08HL168238
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 12/11/2023
PERIOD OF PERFORMANCE END DATE: 11/30/2028

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Advancing the clinical actionability of polygenic scores for coronary artery disease - PROJECT SUMMARY/ABSTRACT: Coronary artery disease (CAD) remains the leading cause of death globally, and the identification of individuals at high risk to target early prevention strategies is a major public health need. Commonly used clinical risk estimators are validated for limited age groups and are poorly calibrated to contemporary populations, limiting their utility. Polygenic scores (PGS) -which quantify inherited risk by summing information from many common sites of DNA variation - hold considerable promise for improving upon available clinical risk estimators, however available PGS for CAD currently lack proper actionability due to limitations of input data, score methodology, and clinical applications. More comprehensive and well-calibrated tools incorporating genetic risk are needed to predict risk earlier in life to enable preventive interventions and reduce morbidity and mortality of CAD. Dr. Patel proposes to develop more generalizable PGS for CAD using large-scale genomic data across multiple populations; to construct clinically interpretable, absolute CAD risk prediction models integrating genetic and non-genetic factors; and to investigate new clinical indications for PGS use utilizing clinical trial data. In Aim 1, Dr. Patel will develop new PGS for CAD by harnessing the principle of burrowing information from functional genomic annotations, cross-ancestry correlation, and cross-trait correlation to refine the effect estimates of genetic variants included in these scores. In Aim 2, Dr. Patel will integrate polygenic risk with clinical risk factors to develop absolute risk prediction models for CAD, which he will then calibrate, validate, and deploy in external datasets. In Aim 3, Dr. Patel will define clinical use indications for PGS using secondary analyses of CAD prevention clinical trials within the context of individuals with inflammatory mediators. The overall goal for this application is to advance the actionability of PGS by addressing their limitations in generalizability, interpretability, and indication. Upon successful completion of these aims, Dr. Patel expects to deliver better-performing and broadly portable CAD PGS, share externally validated, integrated absolute risk prediction models, report utility for PGS use in clinical subgroups for guiding therapies, and nominate inflammatory mechanisms to target in future trials. These endpoints will collectively advance the actionability of PGS models for CAD, moving closer to their clinical deployment for disease prevention. This research will be accomplished in the setting of a comprehensive career development program designed to provide Dr. Patel with the skills needed to become an independent physician-scientist in cardiovascular genomics. This proposal brings together a unique interdisciplinary advisory team of experts in the fields of epidemiology, genomics, statistics, and clinical trials research that will guide Dr. Patel in his transition to scientific independence.


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: 2026 ( Subtotal = $170,323 )
2026	2026	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cardiovascular Diseases Research	000	3	4/3/2026	NON-COMPETING CONTINUATION	$170,323
														Subtotal = $170,323

Issue Date FY: 2025 ( Subtotal = $170,323 )
2025	2025	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cardiovascular Diseases Research	000	2	12/5/2024	NON-COMPETING CONTINUATION	$170,323
														Subtotal = $170,323

Issue Date FY: 2024 ( Subtotal = $170,323 )
2024	2024	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cardiovascular Diseases Research	000	1	12/11/2023	NEW	$170,323
														Subtotal = $170,323

Grand Total All Awards = $510,969

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Advancing the clinical actionability of polygenic scores for coronary artery disease

Award Number: K08HL168238

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 12/11/2023

PERIOD OF PERFORMANCE END DATE: 11/30/2028

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