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Development of Polygenic Risk Scores for Diabetes and Complications across the Life-Span in Populations of Diverse Ancestry

Award Number: U01HG011723
ORGANIZATION: NATIONAL HUMAN GENOME RESEARCH INSTITUTE
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Abstract Large-scale genome wide association studies (GWAS) have identified a large number of genetic variants associated with complex diseases. The aggregation of all the variants that are known to contribute to the disease in the form of polygenic risk scores (PRS) improves the prediction of a range of complex diseases. Most PRS have been developed within European ancestry study samples and have shown to perform poorly in other race/ethnic groups, further exaggerating health disparities across ancestries. As genetic approaches for precision medicine become more popular, there is a critical need to responsively and pro-actively expand access to accurate PRS. Specifically, diabetes, and its associated complications are one of the biggest global health problems of the 21st century. In fact, type 1 and type 2 diabetes (T1D and T2D), gestational diabetes (GDM) and related complications are excellent disease models to study the utility of PRS for predicting heterogenous and complex health outcomes in a setting where dramatic racial/ethnic and socioeconomic disparities exist. Not only are PRS useful to predict T1D and T2D, but they can distinguish between T1D and T2D, and between T2D subtypes. The wealth of existing trans-ancestry GWAS data from diabetes subtypes, complications, and quantitative traits recently generated provides a unique opportunity for constructing highly transferable PRS across populations. To address the disparities in PRS across ancestries, we have assembled a multi-disciplinary team to aggregate and analyze the largest existing genetic data from more than 1.8 M individuals (35% non- European) with T1D, T2D, GDM and glycemia-related complications and quantitative traits to improve the PRS prediction of diabetes and progression across lifespan in diverse ancestries with these Aims: (1) Collection, harmonization and integration of large-scale, multi-ancestry cohorts with diabetes traits across the life-span and genomics for development, training and testing PRS for diverse ancestries; (2) Development of methods to improve PRS prediction in non-European populations by using Bayesian approaches that allow integration of linkage disequilibrium and summary statistics from several ancestries. (3) Development, testing, and comparing performance of PRS for each trait, development of risk prediction tools that integrate clinical and genetic risk factors, and assessment of scenarios where PRS improve the prediction. Accomplishing the aims of this proposal will demonstrate how genomic data can inform more efficient and targeted preventive strategies within healthcare systems and across ethnically diverse populations. Findings are expected to advance precision care of patients with diabetes and related conditions in people of diverse ancestral background and serve as a paradigm for many other complex diseases.


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 = $0 )
2024	2023	BROAD INSTITUTE, INC., THE	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Human Genome Research	000	3	11/22/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $966,817 )
2023	2023	BROAD INSTITUTE, INC., THE	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Human Genome Research	000	3	3/31/2023	NON-COMPETING CONTINUATION	$966,817
														Subtotal = $966,817

Issue Date FY: 2022 ( Subtotal = $984,927 )
2022	2022	BROAD INSTITUTE, INC., THE	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Human Genome Research	001	2	4/22/2022	NON-COMPETING CONTINUATION	$984,927
2022	2021	BROAD INSTITUTE, INC., THE	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Human Genome Research	000	1	12/23/2021	NEW	$0
														Subtotal = $984,927

Issue Date FY: 2021 ( Subtotal = $986,883 )
2021	2021	BROAD INSTITUTE, INC., THE	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Human Genome Research	000	1	6/8/2021	NEW	$986,883
														Subtotal = $986,883

Grand Total All Awards = $2,938,627

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Development of Polygenic Risk Scores for Diabetes and Complications across the Life-Span in Populations of Diverse Ancestry

Award Number: U01HG011723

ORGANIZATION: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

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