Understanding the Functional Contributions and Mechanisms of Type 2 Diabetes Disease-associated Variants (UM1 Clinical Trial Not Allowed) | RFA DK 19 012

Frequently Asked Questions (FAQs) - NIH RFA-DK-19-012 Functional Genomics Projects (Type 2 Diabetes)

1) What is the main goal of this NIH funding opportunity (RFA-DK-19-012)?

The goal is to support large, multi-disciplinary Functional Genomics Projects that move beyond statistical genetic associations and deliver experimental, mechanistic explanations for how type 2 diabetes (T2D) risk/protective variants cause biological effects. The focus is on determining which variants are truly causal, what regulatory elements/genes they act through, and what downstream pathways and disease-relevant phenotypes they influence.

2) What scientific problem is this FOA trying to solve?

Genome-wide association studies and related approaches have identified many DNA variants associated with T2D risk, protection, or progression to complications. However, association signals often do not identify the true causal variant(s), the effector gene(s) or transcript(s), or the molecular mechanisms connecting a variant to disease. This FOA is designed to fill that gap with mechanistic, experimentally grounded answers.

3) What types of projects are expected to be funded?

Projects are expected to be systematic, large-scale, and capable of addressing the landscape of known T2D risk variants. The work is framed around (a) identifying causal variants within associated loci, (b) determining effector transcripts (downstream genes or gene products altered by the variant), and (c) validating that those effector transcripts play a role in T2D biology and its complications.

4) What does "functional genomics" mean in the context of this FOA?

In this context, functional genomics refers to experimental and analytical efforts that connect genetic variation to function: identifying causal variants, linking them to the gene regulatory elements and effector transcripts they influence, and establishing downstream pathway and phenotype impacts relevant to T2D.

5) Does the FOA focus only on variant discovery?

No. The FOA is explicitly intended to move beyond discovery of statistical associations and instead produce mechanistic understanding. That includes pinpointing causal variants, mapping variant-to-gene effects, and validating the biological relevance of effector transcripts and pathways.

6) What are "effector transcripts" as used in this announcement?

Effector transcripts are the downstream genes or gene products whose expression or function is altered by a variant and that help explain how the variant influences T2D-related biology and complications.

7) What is meant by taking a "systematic, large-scale approach"?

It means projects are expected to address T2D-associated variants broadly and comprehensively rather than focusing on a small number of isolated loci. The FOA emphasizes working across the landscape of known T2D risk variants to build more complete functional maps from variant to mechanism.

8) Are network models part of the expected deliverables?

Yes. A major emphasis is on building network models that connect variants to genes, genes to pathways, and pathways to disease-relevant phenotypes. These models are intended to identify key biological readouts and potential points where interventions might be possible in the future.

9) Is this opportunity intended to directly support therapeutic development?

The FOA is designed to generate mechanistic insights, biomarkers, targets, and enabling tools that future translational and therapeutic efforts can build on. It is not positioned as a clinical development or therapeutic trial program itself.

10) Are clinical trials allowed under this FOA?

No. The FOA is explicitly designated as "Clinical Trial Not Allowed."

11) What funding mechanism is used for this opportunity?

The award mechanism is a cooperative agreement (UM1).

12) What does a UM1 cooperative agreement imply for how the project will be run?

UM1 cooperative agreements typically involve substantial NIH scientific involvement and coordination with awardees, rather than a purely investigator-driven, hands-off grant structure. This aligns with the consortium-style organization described in the FOA.

13) Will awardees work as part of a consortium?

Yes. Awardees are expected to be organized into a Consortium with coordination across projects.

14) How does this FOA connect to the Accelerating Medicines Partnership Type 2 Diabetes Knowledge Portal (AMP T2D KP)?

The Consortium is expected to work in coordination with the AMP T2D Knowledge Portal effort so that data generation, standards, and outputs align with shared consortium goals.

15) What are expectations around data sharing and open science?

A key expectation is rapid release of data, tools, and reagents to the broader research community. The FOA emphasizes open science to accelerate follow-on studies by other investigators.

16) What kinds of outputs are expected from funded projects?

Based on the description, expected outputs include experimentally grounded variant-to-mechanism findings, network models linking variants/genes/pathways/phenotypes, and community-accessible data, tools, and reagents released rapidly to enable broader research use.

17) Who is eligible to apply?

Eligibility is broad and includes many types of U.S. organizations: state and local governments; public and private institutions of higher education; nonprofits with or without 501(c)(3) status; for-profit entities other than small businesses; and small businesses. Tribal governments and tribal organizations are also included.

18) Are minority-serving and other specifically named institution types included in eligibility?

Yes. The FOA explicitly welcomes a wide range of institution types, including HBCUs, Hispanic-serving institutions, AANAPISIs, tribally controlled colleges and universities, Alaska Native and Native Hawaiian-serving institutions, faith-based and community-based organizations, and U.S. territories or possessions.

19) Are non-U.S. organizations eligible to apply?

Yes. Non-U.S. entities are eligible to apply according to the information provided.

20) Are foreign components of U.S. organizations allowed?

Yes. Foreign components of U.S. organizations are allowed under NIH policy, enabling international participation where it strengthens the science.

21) What is the listed award ceiling?

The listed award ceiling is $1,500,000.

22) What NIH program area and CFDA listing is associated with this opportunity?

This opportunity is offered by the National Institutes of Health under CFDA 93.847, and it is categorized under health and food/nutrition-related research.

23) What is the application closing date shown in the provided summary?

The original closing date listed is December 3, 2019. This indicates the specific announcement was time-bound and historically dated, even though the provided text summarizes the program design and expectations.

24) What scale and coordination level should applicants plan for?

The UM1 mechanism, consortium structure, coordination with AMP T2D KP, and emphasis on systematic large-scale functional mapping imply sizable, coordinated projects with shared standards and rapid community release of outputs.

25) What disease area and variant types are the focus?

The focus is type 2 diabetes and variants linked to T2D risk, protection, or progression to complications, as identified through genome-wide association studies and related genomic efforts.