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NIH
Posted

PAR-25-255

Developing novel theory and methods for understanding the genetic architecture of complex human traits (R01 Clinical Trial Not Allowed)

Summary

AI-generated

PAR-25-255: Genetic Architecture of Complex Human Traits

Research Focus

This funding opportunity supports development of novel theory and methods to understand how genetic and non-genetic factors shape complex trait variation across individuals, families, and populations. The funder seeks interdisciplinary approaches that move beyond reductive molecular frameworks to account for interactions across biological, social, and ecological scales. Research should employ formal theory, mechanistic models, robust simulations, and validation using large-scale, publicly accessible datasets from populations with diverse environmental exposures, demographics, and geographic histories. The goal is to characterize direct and non-direct, additive and non-additive, and main and interaction effects—enabling more comprehensive understanding of disease propensity and trait presentation.

Applicants must assemble multidisciplinary teams spanning statistical genetics, quantitative genetics, population genetics, evolutionary biology, behavioral ecology, epidemiology, sociology, econometrics, and complex systems science. New data generation is permitted only up to 20% of direct costs; the emphasis is methods and theory development, not primary data collection. When research involves socially sensitive traits or disparities among marginalized or minoritized groups, applicants must address potential harms, misconceptions, and responsible communication to scientific and lay audiences.

At-a-Glance

  • Who can apply: U.S. institutions (specific eligibility details not stated in excerpt)
  • Funding & project length: Not stated
  • Award mechanism: R01 Research Project Grant (clinical trials not allowed)
  • Key dates: Open January 5, 2025; multiple submission deadlines through October 5, 2026; earliest start dates range December 2025–July 2027
  • Best fit for: Quantitative/population geneticists, evolutionary biologists, epidemiologists, and computational modelers developing generalizable methods for complex trait architecture across human health and disease

Key Facts

Deadline

Thu, November 5, 2026

Posted

Fri, November 15, 2024

Award / Year (direct costs)

$250,000

Max Total

$1,250,000

Max Duration

5 years

93.399
93.172
93.242
Modular
Grants.gov
Agency

Keywords

genetic architecture
quantitative genetics
variance decomposition
population genetics
statistical genetics
evolutionary biology
gene-environment interactions
systems epidemiology
pleiotropy
linkage disequilibrium
genotype-phenotype mapping
mechanistic modeling
behavioral ecology
mathematical modeling
non-additive genetic effects
population disparities

Research Areas

MeSH
AnatomyA
Nervous SystemA08CellsA11
OrganismsB
DiseasesC
InfectionsC01NeoplasmsC04Nervous System DiseasesC10Nutritional & Metabolic DiseasesC18Endocrine System DiseasesC19Immune System DiseasesC20Pathological Conditions & SymptomsC23
Chemicals & DrugsD
Amino Acids, Peptides & ProteinsD12Nucleic Acids & NucleotidesD13
Analytical/Diagnostic/Therapeutic TechniquesE
DiagnosisE01Investigative TechniquesE05
Psychiatry & PsychologyF
Behavior MechanismsF01Mental DisordersF03
Phenomena & ProcessesG
MetabolismG03Cell PhysiologyG04Genetic PhenomenaG05Physiological PhenomenaG07Immune System PhenomenaG12Biological PhenomenaG16
Disciplines & OccupationsH
Natural Science DisciplinesH01
Anthropology/Education/SociologyI
Social SciencesI01
Technology/Food/BeveragesJ
Information ScienceL
Information ScienceL01
Health CareN
Population CharacteristicsN01Health Care Quality & EvaluationN05Environment & Public HealthN06
ANZSRC FoR
Biological Sciences31
Bioinformatics & Computational Biology3102Evolutionary Biology3104Genetics3105
Biomedical & Clinical Sciences32
Clinical Sciences3202Immunology3204Neurosciences3209Oncology & Carcinogenesis3211
Earth Sciences37
Climate Change Science3702Physical Geography & Environmental Geoscience3709
Economics38
Applied Economics3801Econometrics3802
Human Society44
Anthropology4401Demography4403Development Studies4404Human Geography4406Sociology4410
Information & Computing46
Artificial Intelligence4602Data Management & Data Science4605Machine Learning4611
Mathematical Sciences49
Applied Mathematics4901Numerical & Computational Mathematics4903Statistics4905
Physical Sciences51

Gotchas (6)

Soft Block
planningprogram team composition

Applications must include a multidisciplinary team spanning natural and social sciences, but the NOFO does not specify minimum team composition, required disciplines, or how to document that this requ

AI

90%

Source Text

Do not include a multidisciplinary team of investigators spanning the natural and social sciences.

Soft Block
discoverymeta ambiguity

Clinical trials are explicitly not allowed under this funding opportunity (R01 Clinical Trial Not Allowed), but the NOFO does not clearly define what constitutes a 'clinical trial' in this context, cr

AI

85%

Source Text

Developing novel theory and methods for understanding the genetic architecture of complex human traits (R01 Clinical Trial Not Allowed)

Soft Block
planningprogram required components

For NCI-specific applications, three specific components are mandatory: (1) integrate germline genetic and environmental data, (2) utilize data across multiple scales, and (3) consider dynamism or mul

AI

90%

Source Text

For applications to be considered responsive to NCI interest, they will need to include all three of the following components: i) integrate germline genetic and environmental data, ii) utilize data across multiple scales (e.g., biological, social, or ecological organization), and iii) consider dynamism or multiple time points in the analysis.

Warning
discoverymeta ambiguity

New data generation is capped at 20% of direct costs, but the NOFO does not specify whether this applies per aim, per year, or to the entire project period. It is also unclear whether 'validation' wit

AI

85%

Source Text

When new data generation is proposed for validation, it is not to exceed 20% of direct costs.

Warning
discoverymeta ambiguity

The NOFO requires applicants to address 'how they will minimize misapplications and misconceptions' and 'communicate potential harms and benefits' for socially sensitive traits, particularly those wit

AI

75%

Source Text

In some cases, certain traits and outcomes may be socially sensitive especially when there are disparities among marginalized or minoritized groups. Applicants should indicate how they will minimize misapplications and misconceptions about their approaches and findings as well as how they will communicate the potential harms and benefits of the research to the scientific community and lay public.

Warning
discoverymeta ambiguity

All genetic and phenotypic data used must be publicly available, with an exception only for new data generation (capped at 20% of costs). However, the NOFO does not clarify whether 'publicly available

AI

80%

Source Text

Any existing data sources used should be publicly available. When new data generation is proposed for validation, it is not to exceed 20% of direct costs. Methods and data (whether derived or new) should be made available to ensure analyses and findings are reproducible.

AI-generated content — verify with the issuing agency’s official FOA/NOFO. Not endorsed by HHS.

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