Tuesday, January 6, 2026 1/6/2026

Leveraging human evolutionary history to improve our understanding of complex disease architecture

Award Number: R00GM137076
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2021
PERIOD OF PERFORMANCE END DATE: 01/31/2027

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Leveraging human evolutionary history to improve our understanding of complex disease architecture - Title: Leveraging human evolutionary history to improve our fundamental understanding of complex disease architecture Abstract: The overarching goal of this research is to improve the applicability of genetic risk predictions within and across human populations by leveraging recent advances in our understanding of human evolutionary history. In Aim 1, I will carry out empirically-guided simulations to investigate how fine-scale substructure in large genome-wide association studies (GWAS; e.g. UK Biobank) biases our inference of complex trait architecture and polygenic risk score prediction. I will leverage these findings to develop statistical and computational tools to correct for such biases. In Aim 2, I will investigate whether recent admixture in humans generates incompatibilities between mitochondrial and nuclear DNA in African Americans. To test this, I will analyze genetic and electronic health record data from the ethnically diverse Penn Medicine Biobank to test whether mito-nuclear discordance—degree of ancestry divergence between mitochondrial and nuclear genomes—is associated with the risk of diseases common among African Americans. Additionally, I will test for selection against mito-nuclear incompatibilities in recently admixed populations. In Aim 3, I will investigate how the practice of endogamy and consanguinity among Pakistanis shapes their disease risk architecture. I will further evaluate the ability and limitations of currently used GWAS methods, which are typically modeled after outbred populations, to infer disease architecture given the complex population structure in Pakistanis. I will improve upon these methods, thereby making GWAS more widely applicable to a diverse set of people. Each of my three aims is independent, yet together they will lead to improvements in diagnosis, treatment, and prevention of human diseases—the overarching mission of the NIGMS. I will learn the skills needed to accomplish these aims with the help of my advisory committee, comprising of Drs. Iain Mathieson, Sarah Tishkoff, Doug Wallace, and Marilyn Ritchie, who are world-class leaders in genetics research. With the training plan that I have outlined and the resources at the University of Pennsylvania, I am confident that the K99 award will help me achieve my goal of becoming an independent scientist in the field of statistical genetics.


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 = $0 )
2026	2025	REGENTS OF THE UNIVERSITY OF MINNESOTA	2221 UNIVERSITY AVE SE STE 100	MINNEAPOLIS	MN	55414	HENNEPIN	USA	Biomedical Research and Research Training	000	5	11/3/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $249,000 )
2025	2025	REGENTS OF THE UNIVERSITY OF MINNESOTA	2221 UNIVERSITY AVE SE STE 100	MINNEAPOLIS	MN	55414	HENNEPIN	USA	Biomedical Research and Research Training	000	5	8/7/2025	NON-COMPETING CONTINUATION	$249,000
														Subtotal = $249,000

Issue Date FY: 2024 ( Subtotal = $259,588 )
2024	2024	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Biomedical Research and Research Training	002	4	6/20/2024	NON-COMPETING CONTINUATION	$24,900
2024	2024	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Biomedical Research and Research Training	001	4	1/31/2024	NON-COMPETING CONTINUATION	$224,100
2024	2023	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Biomedical Research and Research Training	000	3	11/7/2023	EXTENSION WITH OR WITHOUT FUNDS	$10,588
														Subtotal = $259,588

Issue Date FY: 2023 ( Subtotal = $249,000 )
2023	2023	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Biomedical Research and Research Training	000	3	1/25/2023	EXTENSION WITH OR WITHOUT FUNDS	$249,000
														Subtotal = $249,000

Grand Total All Awards = $757,588

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Leveraging human evolutionary history to improve our understanding of complex disease architecture

Award Number: R00GM137076

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/01/2021

PERIOD OF PERFORMANCE END DATE: 01/31/2027

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