Thursday, February 19, 2026 2/19/2026

Polygenic prediction and evolution of complex traits

Award Number: R35GM133708
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: 09/02/2019
PERIOD OF PERFORMANCE END DATE: 11/30/2029

Group Awards By:

View Award Description

Polygenic prediction and evolution of complex traits - The genetic variation that contributes to phenotypic differences among individuals is shaped by mutation, genetic drift and natural selection. Relatively little is known about the relative contributions of drift and selection. On the one hand, in terms of genome-wide variation drift is the stronger force. On the other, this may not be true of phenotypically important variants, of which several examples are known. Ancient DNA provides the ability to directly observe evolution in action over well-defined timescales, and to identify and quantify the effects of selection. As well as explaining how and when unique aspects of our species and populations evolved, this information is important to predict disease risk across the spectrum of human ancestry. Because genetic ancestry is correlated with environment, we do not know whether ancestry- phenotype correlations are causal. The solution is that evidence of recent selection allows us to infer causality – ancient DNA provides information that is independent of observational studies of present-day populations. We propose to develop this in several ways. First, we estimate the contribution of recent (in the past 5-10 thousand years) natural selection to phenotypic variation within Britain. We focus on Britain as a proof- of-concept because of relatively simple demography, access to large samples of ancient and present-day individuals and because so much of our knowledge about the genetic basis of complex traits is derived from this population. However, clearly this only represents a small portion of human variation. Therefore, we will develop approaches to enable studies of natural selection using ancient DNA in populations with more complex demographic histories. We will apply these approaches to data from East Asia and Africa to measure the contribution of natural selection to phenotypic variation and disease risk in these regions. Taking a comparative approach, we will identify common patterns in the response to environmental change such as the independent development of agriculture in these regions. We will contrast patterns of selection in ancient and present-day populations, asking whether it has changed or intensified due to recent shifts in environment. These questions are not restricted to organismal or disease phenotypes. Molecular phenotypes like gene expression, splicing and methylation are critical to understand the functional basis for the effects of GWAS variants and are equally critical to understand the evolution of organismal phenotypes. We will test for recent selection on these phenotypes and identify biological mechanisms that underlie genomic signals of selection. Finally, we will apply these evolutionary insights to the construction of polygenic risk scores to predict disease. Because substantive differences in risk across ancestries are likely driven by selection, identifying selected variants allows us to predict those risks while removing confounding due to genetic variation that is simply correlated with environment from unselected variants. With this approach we aim to construct polygenic scores that are accurate across the spectrum of human genetic ancestry.


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 = $418,275 )
2026	2026	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT STREET	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Biomedical Research and Research Training	000	7	1/7/2026	NON-COMPETING CONTINUATION	$418,275
														Subtotal = $418,275

Issue Date FY: 2025 ( Subtotal = $464,750 )
2025	2025	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Biomedical Research and Research Training	001	6	12/17/2024	COMPETING CONTINUATION	$464,750
2025	2023	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT STREET	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Biomedical Research and Research Training	002	5	5/15/2025	NON-COMPETING CONTINUATION	$0
2025	2023	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Biomedical Research and Research Training	000	5	12/11/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $464,750

Issue Date FY: 2023 ( Subtotal = $402,433 )
2023	2023	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Biomedical Research and Research Training	000	5	6/1/2023	NON-COMPETING CONTINUATION	$402,433
														Subtotal = $402,433

Issue Date FY: 2022 ( Subtotal = $402,433 )
2022	2022	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Biomedical Research and Research Training	000	4	8/23/2022	NON-COMPETING CONTINUATION	$402,433
														Subtotal = $402,433

Issue Date FY: 2021 ( Subtotal = $402,433 )
2021	2021	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Biomedical Research and Research Training	000	3	6/15/2021	NON-COMPETING CONTINUATION	$402,433
														Subtotal = $402,433

Issue Date FY: 2020 ( Subtotal = $401,195 )
2020	2020	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Biomedical Research and Research Training	000	2	6/11/2020	NON-COMPETING CONTINUATION	$401,195
														Subtotal = $401,195

Issue Date FY: 2019 ( Subtotal = $401,195 )
2019	2019	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Biomedical Research and Research Training	000	1	9/2/2019	NEW	$401,195
														Subtotal = $401,195

Grand Total All Awards = $2,892,714

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Polygenic prediction and evolution of complex traits

Award Number: R35GM133708

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: 09/02/2019

PERIOD OF PERFORMANCE END DATE: 11/30/2029

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer