Developing novel theory and methods for understanding the genetic architecture of complex human traits (R01 Clinical Trial Not Allowed) | PAR 25 255

Opportunity Information: Apply for PAR 25 255

The National Institutes of Health (NIH) is inviting R01 grant applications under PAR-25-255 to develop new theory and methodological approaches that improve how researchers understand the genetic architecture of complex human traits. The central aim is not to run clinical trials, but to push forward the conceptual and analytic toolkit used to explain why traits and outcomes vary across individuals, families, and populations. This includes clarifying how genetic factors work on their own and in combination with non-genetic influences such as social environments, ecological contexts, and other layers of exposure and experience that shape human biology and behavior.

A major emphasis of the opportunity is interdisciplinarity. NIH is looking for projects that draw meaningfully from both the natural sciences (for example, genetics, genomics, computational biology, epidemiology, ecology, evolutionary biology) and the social sciences (for example, sociology, demography, economics, psychology, social epidemiology). Proposed work should explicitly recognize that influences on complex traits are often interdependent across multiple scales of organization. In practice, that means applicants are encouraged to move beyond single-factor explanations and instead model how processes at the molecular level may connect to individual development, family structure, community conditions, and broader population patterns, including feedback loops and correlations across these levels.

The NOFO is strongly oriented toward theory, modeling, and rigorous validation, especially using existing large-scale datasets. Competitive applications will typically propose new statistical frameworks, computational methods, or conceptual models, and then demonstrate their performance and usefulness by testing them with available large datasets (for example, large cohorts, biobanks, multigenerational family data, or population-scale resources). The focus is on methods development that is grounded in real data and can be stress-tested for robustness, interpretability, bias, and generalizability across settings and populations. While specific scientific directions are not exhaustively listed in the summary text provided, the overall scope clearly supports work that helps disentangle genetic effects from environmental and social confounding, improves causal inference in complex trait research, and better captures gene-environment interplay and structured population and family relationships.

This is a discretionary funding opportunity using the NIH grant mechanism (Funding Instrument: Grant; Activity Category: Education, Health) and it falls under CFDA numbers 93.172, 93.242, and 93.399. The opportunity was created on 2024-11-15, and the original application due date (closing date) is 2026-11-05. The notice does not list an award ceiling or the expected number of awards in the provided source data, which typically means applicants should refer to the full NOFO text and standard NIH R01 budgeting policies and institute-specific guidance for any practical budget expectations.

Eligibility is broad and includes many types of U.S. organizations and governmental units, such as state, county, city/township, and special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; federally recognized Native American tribal governments; tribal organizations that are not federally recognized; public housing authorities/Indian housing authorities; nonprofits with or without 501(c)(3) status (other than institutions of higher education); for-profit organizations (other than small businesses); and small businesses. The NOFO also highlights additional eligible applicant categories, including Alaska Native and Native Hawaiian Serving Institutions, AANAPISIs, Hispanic-serving Institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), eligible federal agencies, faith-based or community-based organizations, U.S. territories or possessions, regional organizations, and non-U.S. entities (foreign organizations). Taken together, this signals an intent to encourage a wide range of institutions and perspectives, including those with strong community ties and those outside the United States, as long as the proposed work aligns with NIH rules and the scope of the announcement.

In plain terms, this grant is aimed at researchers who want to build the next generation of models and methods for complex trait genetics, where "complex" is taken seriously: traits arise from many genes, many environments, and the ways these influences cluster within families and societies. NIH is seeking projects that can better represent that reality mathematically and computationally, and that can demonstrate value by applying and validating the new approaches in large, existing datasets, ultimately improving how the field explains variation in human traits across diverse populations and contexts.

• The National Institutes of Health in the education, health sector is offering a public funding opportunity titled "Developing novel theory and methods for understanding the genetic architecture of complex human traits (R01 Clinical Trial Not Allowed)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.172, 93.242, 93.399.
• This funding opportunity was created on 2024-11-15.
• Applicants must submit their applications by 2026-11-05. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

Apply for PAR 25 255

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