From Genomic Association to Causation: A Convergent Neuroscience Approach for Integrating Levels of Analysis to Delineate Brain Function in Neuropsychiatry (Collaborative R01) | PAR 17 252

FAQs: NIH PAR-17-252 (Collaborative R01) - From Genomic Association to Causation

1) What is the focus of NIH funding opportunity PAR-17-252?

PAR-17-252 supports neuropsychiatric research that moves beyond statistical genomic associations and toward credible causal (or well-justified probabilistic) explanations of how biological variation leads to brain function changes and behavioral outcomes relevant to mental illness. The intent is to build coherent, testable models that connect genetics to mechanism and ultimately to psychopathology-relevant phenotypes.

2) What problem is this FOA trying to solve?

Large-scale genomic studies have generated many gene-to-trait statistical links for psychiatric traits, but those links often do not explain underlying mechanisms. This FOA targets that gap by funding projects that explicitly connect multiple, adjacent biological levels of analysis into an explanatory framework that can be tested and refined.

3) What does "From Genomic Association to Causation" mean in practice?

It means projects should start from genetic signals (or a meaningful genetics component) and develop mechanistic or probabilistic accounts of how that variation influences downstream biology, neural organization, and behavior. The goal is a defensible explanation that can be evaluated empirically, rather than a purely correlational or descriptive result.

4) What is meant by Convergent Neuroscience (CN) in this announcement?

Convergent Neuroscience refers to research that integrates more than one discipline and more than one measurement scale or biological level. Under this FOA, proposals should connect contiguous layers of analysis (for example, gene to molecule, molecule to cell, cell to circuit, circuit to systems, and systems to behavior) into a coherent and testable model.

5) Does the FOA require a specific number of levels of analysis?

The FOA does not mandate an exact number of levels. However, it signals that stronger applications will typically link at least three contiguous levels of analysis and include a meaningful genetics component consistent with the "genomic association to causation" theme.

6) What counts as "contiguous" or "adjacent" levels of analysis?

"Contiguous" means the project should explain how measurable properties at one level contribute to measurable, quantifiable properties at the next level. Examples include gene to molecule, molecule to cell, cell to circuit, circuit to systems, and systems to behavior. The emphasis is on principled linking across neighboring layers rather than jumping levels without a clear bridge.

7) What types of outcomes or phenomena are expected to be explained?

The FOA emphasizes neuropsychiatry and the delineation of brain function in relation to mental illness. It specifically highlights complex behavioral outcomes, including cognitive and affective processes often disrupted in neuropsychiatric conditions, as key endpoints that should be connected back to biological and neural mechanisms.

8) What makes this a "Collaborative R01"?

This opportunity emphasizes non-superficial collaboration. Teams are expected to be highly synergistic and inter- or transdisciplinary, working together to develop or extend conceptual frameworks and theoretical approaches that connect levels of analysis in a principled way, rather than simply dividing tasks or exchanging data.

9) What kinds of expertise does NIH explicitly want on the team?

In addition to neuroscience expertise, the FOA explicitly highlights "orthogonal" fields from the physical sciences and quantitative disciplines. Examples named include data and computational science, physics, engineering, and mathematics, with the expectation that these disciplines contribute to the integrated framework and modeling approach.

10) Are computational models required, and what kind?

Yes, a major deliverable described in the FOA is the creation of explanatory computational models that bridge contiguous levels of analysis. These models are expected to go beyond descriptive analytics and embody mechanistic or probabilistic hypotheses about how biological processes scale into circuit or systems function and then into behavior.

11) What does the FOA mean by "explanatory" rather than "descriptive" modeling?

Descriptive approaches summarize patterns in data, while the FOA is looking for models that encode a hypothesis about how and why effects propagate from one level of analysis to the next. In other words, the model should represent proposed mechanisms or probabilistic causal structures that can generate testable predictions.

12) Is experimental validation expected?

Yes. The FOA stresses validation of frameworks, theories, and computational models through experimental approaches. Projects should be designed so that model predictions can be checked empirically, allowing teams to refine models and strengthen causal inference about biological underpinnings of psychopathology.

13) What does the FOA suggest about the role of genetics in proposed projects?

Although the FOA does not prescribe a single genetics strategy, it clearly expects a meaningful genetics component to remain central to the study design, consistent with the goal of moving from genomic association toward causation (or well-justified probabilistic explanations).

14) What expectations exist for data and resource sharing?

The FOA includes a community-building expectation: projects should include a robust plan for sharing data and other resources so that outputs are reusable beyond the original team. While specific repositories or standards are not detailed in the provided text, the intent is to generate well-documented shared resources that strengthen the broader convergent neuroscience community.

15) What kinds of shared outputs are implied by "resources"?

The FOA implies reusable outputs such as datasets, analytic pipelines, model code, derived measures, and other tools that can support additional research beyond the funded project. The overall expectation is that projects contribute to a shared framework of resources for the field.

16) What is the scientific "end-to-end" vision NIH is encouraging?

NIH is encouraging projects that build experimentally testable explanations that begin with genetic signals and move through biological organization and neural function to behavior. The most competitive projects are expected to connect multiple adjacent levels of analysis, formalize those connections in computational/theoretical models, validate them experimentally, and share reusable outputs.

17) What is the award ceiling listed for this opportunity?

The source information lists an award ceiling of $500,000.

18) What is the CFDA number and domain for this opportunity?

This is a discretionary NIH grant in the health domain with CFDA 93.242.

19) What dates are associated with this FOA in the provided information?

The provided information lists a creation date of 2017-04-11 and an original closing date noted as 2019-05-07.

20) Who is eligible to apply?

Eligibility is described as broad. It includes public and private institutions of higher education; nonprofits (with and without 501(c)(3) status); for-profit organizations (other than small businesses); small businesses; and various government entities (state, county, city/township, special districts), as well as tribal governments and tribal organizations.

21) Are minority-serving institutions specifically encouraged?

Yes. The FOA explicitly highlights additional eligible applicants NIH wants to encourage, including minority-serving institutions such as HBCUs and Hispanic-serving institutions, as well as Alaska Native and Native Hawaiian Serving Institutions, AANAPISIs, and tribally controlled colleges and universities.

22) Are faith-based or community-based organizations eligible?

Yes. Faith-based or community-based organizations are explicitly listed among the additional eligible applicants NIH wants to encourage.

23) Can organizations in U.S. territories or possessions apply?

Yes. U.S. territories or possessions are explicitly listed among the additional eligible applicants NIH wants to encourage.

24) Are foreign (non-U.S.) organizations eligible?

Yes. Non-U.S. entities (foreign organizations) are explicitly mentioned as eligible in the provided information.

25) Are federal agencies or regional organizations eligible?

Yes. The provided information includes regional organizations and eligible federal agencies among eligible applicants.