Next Generation Genetic Association Studies (U01) | Apply Online

Frequently Asked Questions (FAQs)

What is the name of this funding opportunity?

The opportunity is called "Next Generation Genetic Association Studies (U01)" and is identified as RFA-HL-11-006.

Which agency and institute offered this opportunity?

This was an initiative of the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health (NIH).

What is the main purpose of this program?

The program was designed to move genetic association research beyond statistical links by adding a strong functional layer to genome-wide association study (GWAS) results. Funded projects were expected to connect naturally occurring human genetic variation to measurable changes in biological pathways and networks, using experimentally tractable, cell-based disease models tied back to real patient genotypes and clinical phenotypes.

How is this different from a typical GWAS follow-up effort?

Instead of stopping at a list of associated DNA variants, the emphasis was on determining what those variants actually do in relevant human cell types. The expectation was to use cellular reprogramming and modern molecular and functional assays to test mechanistic hypotheses that explain how GWAS-implicated variants alter cellular behavior and disease-relevant processes.

What diseases or research areas were in scope?

The work was expected to focus on heart, lung, blood, and sleep (HLBS) related conditions, using cell types and models that are relevant to these areas.

What is the role of induced pluripotent stem cells (iPS cells) in this program?

iPS cell technology was a central feature. Applicants were encouraged to take human samples, reprogram them into iPS cells, and then reliably differentiate those iPS cells into disease-relevant tissues and cell types for HLBS research. These iPS-derived cells served as the functional testbed for evaluating the effects of human genetic variation.

What kinds of experiments or data generation were expected?

Projects were expected to combine iPS-derived cellular models with molecular profiling methods (for example, genomic and other high-dimensional assays) and/or cellular functional assays. The goal was to generate data that can support direct tests of specific mechanistic hypotheses about how GWAS-implicated variants influence cellular pathways and networks.

Was data integration with existing human datasets part of the expectation?

Yes. A key goal was integrating cellular-system data with existing genotypic datasets and corresponding clinical phenotypes, creating a bridge between population genetics findings and experimentally measurable biology.

What award mechanism was used?

The program used a U01 cooperative agreement mechanism.

What does a U01 cooperative agreement imply for how the project is run?

A U01 cooperative agreement indicates that NHLBI anticipated an active partnership role rather than a fully hands-off, investigator-only approach.

Were multi-PI applications encouraged?

Yes. The announcement explicitly encouraged multi-PI applications, reflecting the multi-disciplinary nature of building and operating an end-to-end platform spanning reprogramming, differentiation, scaling, and functional testing.

What types of expertise would a competitive team typically need?

Based on the program description, competitive teams would typically include strengths in iPS reprogramming, differentiation biology for relevant HLBS cell types, scalable lab automation or production workflows, genomics and molecular profiling, statistical genetics and GWAS interpretation, computational biology, and clinical or translational expertise to maintain disease relevance and linkage to human phenotypes.

How was the project structure organized?

Applications were structured as a single, phased program that could span up to three sequential phases. Each phase built toward a high-throughput, hypothesis-testing platform connecting GWAS signals to functional effects in human cells.

What was the focus of Phase I?

Phase I emphasized technology development, including generating iPS cells from human samples and establishing differentiation protocols into specific disease-relevant cell types.

Was Phase I always required?

No. Phase I was not automatically required. Whether it was needed depended on whether the applicant could already demonstrate validated and reproducible differentiation for the targeted cell type(s).

What was the focus of Phase II?

Phase II focused on scaling: taking what was proven earlier and building a higher-throughput system capable of producing differentiated cells from iPS cells across population samples. This scaling was positioned as essential for mapping functional impacts of genetic variation across many donors and genotypes.

What was the focus of Phase III?

Phase III was the functional hypothesis-testing phase. Using the platform created in earlier phases, investigators were expected to test GWAS-driven functional hypotheses directly in cell-based disease models to reveal how genetic variants influence cellular networks and disease-relevant processes.

Could applicants start at Phase II instead of Phase I?

Yes. Applicants could propose the full Phase I through Phase III sequence, or, if iPS and differentiation capabilities were already mature and reproducible, they could start at Phase II and continue through Phase III.

Why did the program allow teams to skip Phase I?

The flexibility was meant to avoid forcing well-prepared teams to re-develop tools they already had, while still ensuring that groups working with less-established cell types or protocols invested in the validation needed for credible population-scale and mechanistic studies.

When was this funding opportunity posted?

The opportunity was posted on March 15, 2010.

What was the application closing date?

The original and current closing date was June 15, 2010.

When was the opportunity archived?

The archive date was July 16, 2010.

What was the estimated total funding level for the initiative?

NHLBI listed an estimated total funding level of $76,000,000.

Was cost sharing or matching required?

No. The opportunity did not require cost sharing or matching.

What types of organizations were eligible to apply?

Eligibility was described as broad. It included many categories of U.S. organizations such as public and private higher education institutions, nonprofits with and without 501(c)(3) status, small businesses, for-profit entities other than small businesses, and various levels of government (including city, county, and state).

Were any special institution types explicitly included in the eligibility description?

Yes. The eligibility notes included categories such as HBCUs, Hispanic-serving institutions, tribally controlled colleges and universities, Alaska Native and Native Hawaiian serving institutions, faith-based and community-based organizations, and U.S. territories or possessions.

Were non-U.S. organizations eligible?

Yes. The eligibility notes indicated that non-U.S. (foreign) organizations and regional organizations were included, as described in the eligibility information.

What was the intended outcome of the program overall?

The intended outcome was to build end-to-end capabilities that start with human genetic discoveries and move toward experimentally testable biology, using iPS-derived, disease-relevant human cells as the functional platform. The goal was mechanistic insight into cellular pathways and networks with clear links back to human genotype and clinical phenotype information in HLBS-related disease areas.