Department of Health and Human Services
National Institutes of Health (NIH)
National Human Genome Research Institute (NHGRI)
Funding Opportunity Title
Centers for Common Disease Genomics (UM1)
UM1 Research Project with Complex Structure Cooperative Agreement
- February 25, 2015 - Notice of Clarification of Language in RFA-HG-15-001. See Notice NOT-HG-15-022.
- February 10. 2015 - Notice of Clarification of Language in RFA-HG-15-001. See Notice NOT-HG-15-020.
- January 16, 2015 - Notice of Applicant Information Webinar for RFA-HG-15-001. See Notice NOT-HG-15-015.
Funding Opportunity Announcement (FOA) Number
Companion Funding Opportunity
Only one application per institution is allowed as defined in Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)
Funding Opportunity Purpose
The National Human Genome Research Institute (NHGRI) seeks to fund a collaborative large-scale genome sequencing effort to comprehensively identify rare risk and protective variants contributing to multiple common disease phenotypes. This initiative will explore a range of diseases with the ultimate goal of undertaking variant discovery for enough different examples of disease architectures and study designs to better understand the general principles of genomic architecture underlying common, complex inherited diseases; understand how best to design rare variant studies for common disease; and develop resources, informatics tools, and innovative approaches and technologies for multiple disease research communities and the wider biomedical research community.
December 12, 2014
Open Date (Earliest Submission Date)
March 7, 2015
Letter of Intent Due Date(s)
March 7, 2015
Application Due Date(s)
April 7, 2015, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on this date.
Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.
AIDS Application Due Date(s)
Scientific Merit Review
Advisory Council Review
Earliest Start Date
April 8, 2015
Due Dates for E.O. 12372
Required Application Instructions
It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.
Table of Contents
- Part 1. Overview Information
- Part 2. Full Text of the Announcement
- Section I. Funding Opportunity Description
- Section II. Award Information
- Section III. Eligibility Information
- Section IV. Application and Submission Information
- Section V. Application Review Information
- Section VI. Award Administration Information
- Section VII. Agency Contacts
- Section VIII. Other Information
The National Human Genome Research Institute (NHGRI) seeks to fund several Centers for Common Disease Genomics (CCDG), which will constitute a collaborative large-scale genome sequencing effort to comprehensively identify rare risk and protective variants contributing to multiple common disease phenotypes. This initiative will explore a range of diseases with the ultimate goal of undertaking variant discovery for enough different examples of disease architectures and study designs to better understand the general principles of genomic architecture underlying common, complex inherited diseases; understand how best to design rare variant studies for common disease; and to develop resources, informatics tools, and innovative approaches and technologies for multiple disease research communities and the wider biomedical research community. This program will pursue these examples as comprehensively as possible---emphasizing whole genome sequencing over whole exome sequencing where feasible--- and also will drive the state-of-the-art in identifying rare variants underlying common disease. In this context, comprehensiveness will be considered broadly, including consideration of, e.g. statistical power, exploring a range of different populations (including those that are currently under-represented in sequencing studies), study designs, and the extent of the genome studied (e.g., whole genomes versus whole exomes). The program will include analysis of the data in order to identify variants associated with risk of, or protection from, disease, and to discern general principles of complex disease architecture. NHGRI expects that this program will need to be highly collaborative between investigators funded by this and other NHGRI programs that span the continuum from inherited disease variant discovery through understanding variant function. NHGRI also anticipates that this program will require a high degree of collaboration with researchers with an interest in particular inherited diseases, both to identify appropriate sample sets (collection of new samples will not be funded under this initiative), to provide domain expertise for study design and analysis, and to ensure that the data and ability to use it are widely disseminated as resources.
Rare variants and common disease
A comprehensive understanding of the genomic variants underlying inherited disease phenotypes is a key goal for biomedicine, with consequences for understanding diseases affecting hundreds of millions of people. It is widely anticipated that a comprehensive account of variants affecting risk for, and protection from, disease phenotypes will afford improved diagnosis, prognosis, and disease management, and even implicate targets for development of new treatments. In addition to these biomedical questions, there remain large gaps in our understanding of the basic biology of disease that can be substantially closed with the aid of a concerted effort focused on identifying and characterizing disease-associated variants. These include basic questions about the underlying architecture of inherited diseases, e.g., considerations of the number, type, frequency and effect size of variants; how those differ between different populations; how they relate to phenotype, including severity, age-of-onset, and relationship to evolutionary selection. Moreover, this focus has potential connections to even more fundamental questions, for example about gene interactions and pathways as variants are discovered that implicate sets of genes in common phenotypes, or for gene regulation by identifying noncoding sequence variation associated with a phenotype.
These connections between basic disease biology and the genomics of inherited disease span a substantial part of the National Human Genome Research Institute's strategic plan (Charting a course for genomic medicine from base pairs to bedside; see http://www.genome.gov/27543215), and consequently a number of ongoing major NHGRI programs, including those funding projects seeking to understand the function of genomic regions and variants; to those funding projects seeking to understand how best to apply knowledge about genomic variants in the clinic. This FOA, together with a related initiative (RFA-HG-15-002; Centers for Mendelian Genomics), conceptually lie between those other programs and are intended to complement them.
Over the last decade, genome–wide association studies have been (and continue to be) effective in identifying more common disease-associated variants, but genome sequence data are required to identify the full spectrum of the genetic contributions to common diseases, particularly rare variants. GWAS and genome sequencing studies done so far on common, complex diseases have yielded a number of general lessons that are important considerations for this initiative, including:
- Large sample sets may be needed to attain sufficient statistical power to identify rarer variants of lower effect. Current analyses suggest that as many as 25,000 cases and 25,000 controls could be required for each disease study focused on analysis of protein-coding regions. Analysis of noncoding sequence variants could require even larger sample numbers because they are expected to be more difficult to interpret (e.g., smaller effect size; less clear assignment to gene function).
- Variants occur at different frequencies in different populations. This is not only important for understanding inherited diseases in different populations, but also must be considered in designing specific studies-- some risk variants may be much easier to detect in some populations.
- More understanding is needed about the advantages of different study designs. The term "design" has a very wide connotation here, and includes considerations of power and sample number; phenotypes and endophenotypes; disease sub-groups/extremes; case/control and cohort studies; risk-raising and protective variants; studies within families or extended related groups; studies in different populations, especially those of non-European ancestry that are under-represented in current studies; replication studies; parallel studies in well-selected animal models of common disease; and other considerations. Because different diseases have different underlying architectures, different study designs may be appropriate in different contexts. In addition, multiple complementary designs may be needed for individual diseases. Finally, large studies can be costly, and there is a need to develop efficient study designs. Considerations about design are also bound up with considerations about sequencing technology, data production cost, and analysis methods.
- Nearly all types of epidemiologic study designs can yield valuable samples for genomic sequencing studies, including cross-sectional, case/control, longitudinal (whether nested within prospective cohorts or not), and prospective cohort designs and clinical trials. As a practical matter, the large numbers of affected cases needed for genome sequencing studies of common diseases typically involve large case-control or cohort studies or a combination of both. Studies of quantitative traits, in contrast, more commonly involve cross-sectional or prospective cohort studies providing a wide distribution of such traits. However, regardless of the initial epidemiological study design under which samples were collected, the availability of high quality and extensive phenotypic information on each study subject is a critical practical and scientific consideration that can be at least as important as the original design. Where relevant, environmental characterization of the persons from whom samples are drawn should be available. Preexisting or newly obtained participant consent should allow for these investigations. The ability to carry out long-term follow up with study participants is desirable. For these reasons NHGRI intends to support studies most likely to meet the goals of this RFA (comprehensively identifying rare variants contributing to common disease phenotypes) regardless of the study design under which samples were collected.
- In the recent past, technology, practical considerations, and a general lack of ability to analyze noncoding regions have limited large, common disease/rare variant studies to whole exome studies. At the time this RFA is being written, it is increasingly apparent that genome sequence data production costs (see below) will decrease to the point where whole genome sequencing of very large sample numbers will become feasible, although this will need to be done by large centers or other efforts with substantial centralized resources.
- Identifying structural variants by analyzing short-read sequence data is not a solved problem, despite the known importance of this variant type in common disease. The development of technologies that produce longer sequence reads will make this an easier problem to solve.
- More work is needed on analysis methods for associating variants with phenotypes. This is connected to considerations about study design.
- Much more work is needed on developing analysis methods and resources to understand the functional significance of variants---particularly noncoding (NHGRI has initiated a program specifically in this area: see https://grants.nih.gov/grants/guide/rfa-files/RFA-HG-13-013.html). Sequence variants that implicate sets of genes underlying an associated phenotype provide some insight into the biology of disease, but this is inconclusive without further functional (optimally, experimental) validation. As resources that catalog gene and genome function grow over time, the ability to make functional inferences based on variant association data will improve. There is likely to be value in encouraging connections between variant discovery and improvement of functional validation.
- Common disease and Mendelian disease architectures are on a continuum that has to be recognized; however for practical reasons NHGRI has decided to pursue Mendelian disorders through a separate mechanism.
- A small number of very large studies seeking to find rare variants underlying common disease are well under way (mostly by studying exomes), but so far we have no examples of studies that are comprehensive (see discussion below).
Continuing to improve the state-of-the-art in genome sequencing is a critical element of this initiative, as it has been with past large-scale sequencing and analysis programs funded by NHGRI. Commercial development of sequencing platforms now largely (but not exclusively) drives sequencing costs. However, cost is not the only consideration: data quality, utility, and suitability to address particular scientific questions at scale are at least as important, as is the ability to integrate new platforms into an overall data production and analysis pipeline to achieve large-scale discovery. NHGRI believes that adoption of new platforms and adaptation and application to relevant, large-scale projects is a key capability of its high-throughput sequencing initiatives. There have been numerous past examples of this within the NHGRI program, including: sequencing library insert sizes were optimized to yield better structural variant detection or assembly; new preparation methods had to be developed in order for some samples to be used on available platforms; genome coverage parameters were systematically tested and modified to yield high-quality data in specific applications; multiplexing methods were developed in order to efficiently carry out sequencing of select genomic regions in thousands of samples; variant calling tools were benchmarked, compared, optimized, and combined. Each of these modifications---carried out in the context of large-scale discovery projects--- was accompanied by changes in sequencing informatics and analysis pipelines, and each represents knowledge about applications of genome sequencing that have been useful to the wider community. At a higher level, the NHGRI-funded genome sequencing grantees have had the flexibility to adopt and optimize multiple new technology platforms over time in consideration of scientific, quality, and practical factors. This includes adoption of the latest, most efficient high-throughput short-read platforms but also long-read and other special-purpose platforms e.g. to improve genome assemblies.
Over the quarter ending in September 2014, the average cost of a 30X coverage short-read whole human genome sequence within the NHGRI Large-Scale Sequencing and Analysis Program was just under $5000 (http://www.genome.gov/sequencingcosts/); a whole exome approximately one-tenth of that amount. Here, costs include reagents, personnel, amortized equipment, management, utilities, data processing, data submission, and indirect costs. Because the studies that will be the subject of this initiative will be large, and the funding, though substantial, will be limited compared to the task, it is critical that the ongoing program---as have its predecessors--- realize significant cost reductions over time in order to have a high confidence of attaining its goals.
Scientific goals and objectives. This FOA aims to fund a collaborative large-scale genome sequencing effort to identify risk and protective variants contributing to multiple specific common disease phenotypes; to explore a range of diseases with the ultimate goal of doing this as comprehensively as possible within the evolving state-of-the-art for enough different disease architectures and study designs to understand general principles of how best to design rare variant studies for common disease; to better understand the genomic architecture underlying inherited disease; and to develop resources for multiple disease research communities and the wider biomedical research community.
This FOA will support work of a scale and scope that will be as comprehensive as possible (see discussion below) for several diseases. The research network composed of investigators funded through this FOA will study several common diseases (see Selecting Projects, below) comprising a range of disease architectures that encompass, for example, differences in the number, population frequency, type, and effect size of underlying variations and that likely correlate with features of the disease phenotype, such as severity and age of onset. Within the limits of the funding provided, it is anticipated that at least five to ten architecturally diverse disorders will be explored comprehensively over the course of the program. A variety of study designs will also be encouraged including creative designs that may be more efficient (for example, choosing appropriate populations for study, in which some variants are enriched in frequency). Given NHGRI’s unique role in propelling advances in large-scale sequencing, efforts funded in response to this FOA will be confined to questions that can only be answered at very large scales.
In addition to sequence data production, innovative analyses will be required to provide useful insights into the major questions about common disease genomic architecture outlined above; that is, to discover genome sequence variants underlying specific common diseases and to gain general insights into the genetic architecture and biology of common disease.
Finally, one scientific objective of this initiative is that the end result should be more than just quantitative, that is, more than just adding more and more variants of lower frequency and effect size as power increases. Rather, the program should deliver clear qualitative insights into the scientific questions considered. These might include, for example, understanding and establishing the value of the approach, and limits of our ability to understand common disease, in the context of different disease architectures, or practical limits, or other factors. Another example would be clearly defining "stopping points" for common disease sequencing studies, balancing scientific and practical considerations. In addition, it is an objective of this FOA that studies be designed so that even a negative result is informative.
Foundational goals and objectives. In addition to the scientific objectives above, the program has the following foundational goals all generally aimed at providing resources for the larger community and improving the state-of-the-art in genome sequencing and analysis:
- Developing durable data resources for the research community, including high-quality genome sequence and variant data (along with existing phenotype and other data) for several large common disease studies and potentially a set of common controls.
- Disseminating knowledge through collaborations with multiple communities; in this case, each disease project will represent an opportunity to exchange and disseminate knowledge about design, methods, analyses, and limitations of genomic sequencing approaches.
- Making technological innovations to optimize cost and quality and expand to novel applications (e.g., non-standard samples, improvement of genome sequence assemblies, etc.).
- Evaluating, adopting, optimizing and integrating new genome sequencing platforms.
- Developing data handling and analysis platforms compatible with advances in DNA sequencing and computer hardware and software.
- Improving and comparing genome analysis methods and informatics tools in the context of a research network within and across NHGRI programs.
- Serving as a locus for the development and refinement of policies and practices about genomic data collection and deposition.
Additional features (also to be addressed in the application) that will aid in attaining the main goals above include:
- Access to state-of-the-art genome sequencing platforms over the life of this program, and the ability to evaluate, adopt, integrate, and optimize new sequencing and sequence analysis technologies as they evolve.
- Capability to develop computational sequence analysis methods and pipelines in tandem with the data production, for the purposes of improved and more efficient analysis of the data towards the goals of this initiative.
- Capability to work on multiple projects with different phenotypes, including access to multiple different sample sets, and ability to develop collaborations with multiple disease communities.
- Flexibility to expand sequencing capacity significantly (e.g., 1.5-fold or more) to accommodate emerging opportunities that may arise for the study of common disease.
- Capability to undertake projects that are compelling and broadly useful, but may not be directly related to studies of a specific disease (e.g., population variation studies).
- Potential to collaborate with other investigators to pursue more functional follow-up studies to enhance analysis and/or validate findings. This FOA provides only very limited funds for functional follow-up studies (see Pilot Collaborations).
- Capability to bring to bear other technologies that are used in genomic analysis, and which could be directly relevant to disease variant analyses. These could include, for example, genotyping, or production and integration of other data modalities that can readily be generated with genome sequencing platforms (e.g., transcriptomes and epigenomes) and that are directly relevant to understanding the role of variation in common disease. It is expected that the great majority of data generation funded under this FOA will be genome sequence data produced from human samples, but some other, well-justified and limited studies may be proposed as an adjunct to genome sequencing studies.
- Capabilities touse creative means to add value or take alternative, better approaches to identify variation underlying common disease; for example disease variant discovery in well-chosen non-human model organisms, or phenotypes that are not strictly disease phenotypes. Again, this is expected to be an adjunct to genome sequencing studies on samples from humans.
- Potential to identify other sources of funding or to otherwise increase the size or number (comprehensiveness) of studies that can be done under the broad intentions of this FOA. However, co-funding or cost-sharing is not a requirement.
- Plans for and success in dissemination/deposition of genomic datasets, computational tools, project design "know-how", etc.
With this FOA NHGRI seeks to fund a number (5-10) of examples of large, comprehensive variant discovery studies to produce sufficient data to test ideas about sample number requirements, disease architecture, optimum study design, etc. NHGRI is uniquely positioned to undertake studies that are as complete as possible given the state-of-the-art, with adequate power to detect rare variants. A working definition of "comprehensiveness" is provided below. The notion of what constitutes a comprehensive study
Because the notion of "comprehensiveness" is vague, it is useful to begin by considering it as an ideal. A comprehensive common disease variant association study would encompass at least the following "element":
- The identification of all associated (risk-raising and protective) variants (both coding and noncoding) down to a specified but arbitrary low frequency and effect size, in a representative set of diverse human populations, for a particular phenotype, including replication. Identification of associations will require statistical analyses, and may require computational functional analysis (for example, to cluster implicated genes by function). A more extended definition of "comprehensiveness" could include other elements, such as:
- Further computational and experimental analyses of function, including collection of, and correlation with, high-throughput datasets other than genome sequence data (e.g., transcriptome, proteome, metabolome; DNA methylation; etc.), but also e.g. functional validation in model systems; and beyond;
- Gene by environment (GXE) analysis enabled by starting with samples for which there are high-quality exposure data;
- Follow-up in large phenotyped population studies to understand modifiers of risk associated with sequence variants;
- Microbiome studies to accompany rare variant sequencing studies especially for certain diseases;
- Studies correlating variation discovered with clinical outcomes;
- and perhaps others.
" The identification of all associated (risk-raising and protective) variants (coding and noncoding) down to a specified but arbitrary low frequency and effect size, in a representative set of diverse human populations, for a particular phenotype, including replication. Identification of associations will require statistical analyses, and may require computational functional analysis (for example, to cluster implicated genes by function)."
Starting from this point, applications responding to this FOA, in addressing the notion of comprehensiveness, should consider the following points, each of which is a critical consideration for the goals of this FOA:
- Comprehensiveness must consider sample number and statistical power. The allele frequency and effect sizes that should be attained are unstated here, and moreover the limits to attaining them will vary for different diseases and are not actually known for any disease. Establishing a better understanding of these parameters, and using the resulting information to improve the state-of-the-art, is a major intent of this initiative.
- One way to consider "comprehensiveness" is to define a stopping point for a study based on diminishing returns, such as saturation for alleles, or saturation for genes. Is this useful? Are there better alternatives?
- Comprehensiveness must consider the balance of examining the whole genome and the ability to assess noncoding variants, vs. limiting study to the exome, for which it is currently more practical to sequence enough samples to attain power and to analyze them. With this FOA, NHGRI emphasizes whole genome sequencing (WGS), and seeks to make it increasingly practical over the term of this initiative, both in order to drive the state-of-the-art in genome sequencing, and to enable the study of noncoding variation.
- Comprehensiveness should consider populations to be studied. This initiative cannot fund work on all populations for every study but consideration of comprehensiveness must take into account the study of diverse populations, especially those of non-European ancestry that are under-represented in current studies, as a matter of science. Are there representative subsets of populations? Are there other rationales for population sampling that would increase comprehensiveness efficiently?
- Comprehensiveness should consider comparing different project design strategies for their scientific utility (if not within a single funded application, then across the entire program). Also, more efficient designs would allow more studies to be done. One potential outcome of this program that could reduce costs might be development and use of common controls.
- Finally, beyond comprehensiveness within a study, this program aims for comprehensiveness in understanding disease variation across a range of different disease architectures. Although this program probably cannot undertake study of a full range of disease architectures, it does aim to study at least five to ten examples that represent a span of disease architectures.
Ultimately, the applicant will be asked to define comprehensiveness in the application (see section IV.2), considering and balancing the scientific and practical issues. We note that some of the points mentioned above (e.g., comprehensiveness of disease architectures) cannot (or cannot solely) be addressed in a single application and will have to be addressed by the program as a whole.
While the main focus of the initiative described in this FOA is centered on element #1 above, NHGRI acknowledges that comprehensive studies could include aspects of the other elements, particularly where they can directly inform function of variants, and can be done using genome sequencing technology (e.g., transcriptomes, methylomes) or using computational analysis.
However, extensive experimental validation, proteome or metabolome data production, GXE studies, clinical applications, and large studies of risk in populations are beyond the direct scope of this FOA. Nonetheless, NHGRI seeks projects whose design anticipates that these further studies could be done either using other funding or through collaborations. For example, ideal samples chosen for study might include those for which subjects can be re-contacted for follow-up phenotyping; samples that have corresponding tissue samples for transcriptomic or proteomic studies; samples for which there are high-quality exposure data, etc. (see Samples, below).
One of the outcomes of this initiative will be data resources of high utility to the biomedical community, both those useful for studying specific diseases, and those e.g., seeking to improve sequence analysis tools, or study population genetics. Therefore, high emphasis will be placed on work on samples that have broad consent for data deposition and general research use, within current NIH policy (http://gds.nih.gov/). This initiative will not fund collection of new samples.
Identifying specific projects
This RFA seeks to fund large centers that have the flexibility to undertake multiple individual common disease projects over the total award period, some of them proposed by applicants (occupying about 40% of overall production capacity), and some chosen by NHGRI. Therefore, this program will use several ways to identify new common disease projects, as outlined below. This is aimed at balancing a number of desirable features, including the practical need to efficiently engage sequencing pipelines towards achieving the goals of the initiative; rigorous review; the ability to identify new projects over the duration of the program; and the ability to engage collaborating communities and their funders. The different ways of selecting projects include:
- First-year projects proposed by applicants (see See IV.2: Content and Form of Application Submission, Instructions for Applicant Submission). Proposed Projects may cover a range of complex (i.e., non-Mendelian) disorders, prioritizing common inherited disease. Germline cancer susceptibility projects will be considered but as a lower priority for NHGRI funding. Tumor sequencing projects will not be considered.
- Projects identified by NHGRI for Year 2 and beyond, through a reviewed mechanism. These may be proposed by, or together with, a funded grantee, or by outside investigators. The procedures and detailed criteria for new projects will be issued separately, and will be timed so that new projects can begin in the second year of the current initiative.
- Projects identified through workshops held in collaboration with scientific disease communities; collaborations with other NIH Institutes and Centers; and NHGRI-identified programmatic priorities, which may be stand-alone projects or collaborations with other NHGRI-funded programs, including those related to functional genomics or clinical applications. These may also include international collaborations.
In general, criteria for selection of projects by NHGRI or through workshops will be similar to those applied to the applications to this FOA (see section VI.4).
In all of these instances, the work will be reconciled with program goals, for example the need to explore a range of disease architectures and project designs.
One long-term objective of this initiative is to begin to connect the discovery and basic characterization of rare variants underlying common disease (element 1 under the discussion of "Comprehensiveness", above) with validation of function (element 2). Yet, this FOA provides only limited scope to pursue that. In addition, this initiative aims to encourage the dissemination of the results to those investigators who are most expert in the biology of disease. In order to stimulate efforts towards these goals, applicants may propose pilot efforts ($200,000 maximum total costs; one pilot per center per year) that extends the "comprehensiveness" of these common disease/rare variant sequencing studies. Pilot Collaborations may only be established with investigators who are not funded otherwise under this award, and who are outside the investigator's academic department, preferably in a different institution. Pilots must propose work that is beyond the immediate scope of this FOA, e.g. on functional analysis. Pilots may include experimental or computational approaches, including development of new approaches. Applicants have the option to propose a pilot for the initial year of the award. New pilots, with new outside investigators, will be proposed with each annual renewal and evaluated administratively. See Section IV.2: Content and Form of Application Submission, Instructions for Applicant Submission.
Leveraging of NHGRI funding
One objective of this program is to foster collaboration with other similar efforts funded by others in order to increase the chances of attaining the program goals. There are two main reasons for this. First, successful comprehensive common disease projects will be of wide interest to communities that are traditionally funded by other institutes. Their inclusion, as collaborators, has the potential to improve the focus and quality of the research, and to help make any resources that result from the program more readily available and useful to those communities. Second, the scope of this initiative is very ambitious compared to the funds provided. Assuming that fully loaded whole genome sequencing costs (plus automated analysis and data processing and storage costs) drop to ~$2000-3000 next year (a figure based on current NHGRI cost tracking data), a single well-powered common disease study of ~50,000 samples could cost $100-150M. In other words only a few such studies could be undertaken by the program in four years. For these two reasons NHGRI plans to strongly encourage collaborations with similar projects, in multiple ways---including, but not limited to, standard collaborations, in-kind (e.g., sequencing capacity) or direct institutional or other contributions---in order to increase the chances of programmatic success.
For these reasons, this program is designed, and will be managed (see Terms and Conditions, Section VI.2) to encourage such collaborations and other innovative ways to fully leverage NHGRI funding. Specifically, based on programmatic progress and other factors likely to increase the chances of success, NHGRI plans to reserve a portion of program funds each year, and may provide these as additional support halfway through the grant year. Factors will include (but are not limited to) the ability to identify additional resources that can be directed towards the program objectives and increase the number, variety, power, extent, etc. of Projects. NHGRI also recognizes its own interest in attracting additional resources to the program and will actively seek direct opportunities for doing so, including seeking co-funding arrangements between NHGRI and other NIH Institutes.
It should be emphasized that the examples provided above (collaborations, sequencing capacity, external or institutional resources) are not intended to be prescriptive, or to exclude other creative means of achieving the same goals, as long as the efforts directly complement the objectives of this FOA. Rather, NHGRI seeks to encourage any additional means to increase the effectiveness of the funds provided for this program.
In addition to the given examples, other factors that could contribute to achieving program comprehensiveness may include reduction in sequencing and data storage costs over time, development of efficient designs, and advancements in other foundational objectives of this program. (Updated February 10, 2015 per issuance of NOT-HG-15-020.)
Diversity action plan
All successful applicants are expected to participate in NHGRI's diversity action plan by applying to PAR-13-063 for the September 25, 2015, due date. Applicants are strongly encouraged to discuss the initial results of their UM1 application with staff before applying for the R25. (Updated February 25, 2015 per issuance of NOT-HG-15-022.)
Participation as part of the NHGRI Genome Sequencing Research Network
Successful applicants to this program will be expected to collaborate effectively with each other to maximize the chances of overall success of the program. For example, some of the projects envisaged here may be very large, and require multiple groups to coordinate e.g. on data production, complementary project designs, and other aspects.
Furthermore, NHGRI plans to solicit and fund a program Coordinating Center and also potentially a separate initiative for analysis activities. These will become components of the NHGRI Genome Sequencing Research Network, along with the Centers for Mendelian Genomics and the CCDG.
In addition, NHGRI recognizes that more extended studies (e.g., function, population risk, GxE, etc.) to identify and characterize variants underlying common disease are likely to fall outside the scope of this FOA, but may fall within the scope of another NHGRI program. Successful applicants are likely to be asked to collaborate with other NHGRI-funded research networks if the scientific opportunity arises to explore an extended study.
Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities.
Application Types Allowed
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards
The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.
NHGRI intends to commit $60M total costs in FY 2016 to fund 2-5 awards.
Application budgets are limited to $40M total costs per year but need to reflect the actual needs of the proposed project.
Award Project Period
The maximum project period is 4 years.
NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.
1. Eligible Applicants
Higher Education Institutions
- Public/State Controlled Institutions of Higher Education
- Private Institutions of Higher Education
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
- Hispanic-serving Institutions
- Historically Black Colleges and Universities (HBCUs)
- Tribally Controlled Colleges and Universities (TCCUs)
- Alaska Native and Native Hawaiian Serving Institutions
- Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)
Nonprofits Other Than Institutions of Higher Education
- Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
- Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)
- For-Profit Organizations (Other than Small Businesses)
- State Governments
- Special District Governments
- Indian/Native American Tribal Governments (Federally Recognized)
- Indian/Native American Tribal Governments (Other than Federally Recognized)
- U.S. Territory or Possession
- Native American Tribal Organizations (other than Federally recognized tribal governments)
- Regional Organizations
Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.
Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.
- Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
- System for Award Management (SAM) (formerly CCR) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
- NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
- eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
- Grants.gov – Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.
Program Directors/Principal Investigators (PD(s)/PI(s))
All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.
Eligible Individuals (Program Director/Principal Investigator)
Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.
For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.
2. Cost Sharing
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
Number of Applications
Only one application per institution (normally identified by having a unique DUNS number or NIH IPF number) is allowed.
The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:
- A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
- A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
- An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).
In addition, the NIH will not accept a resubmission (A1) application that is submitted later than 37 months after submission of the new (A0) application that it follows. The NIH will accept submission:
- To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;
- Of an investigator-initiated application that was originally submitted to an RFA but not paid; or
- Of an application with a changed grant activity code.
1. Requesting an Application Package
Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the "Apply for Grant Electronically" button in this FOA or following the directions provided at Grants.gov.
It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.
For information on Application Submission and Receipt, visit Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.
Letter of Intent
Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.
By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:
- Descriptive title of proposed activity
- Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
- Names of other key personnel
- Participating institution(s)
- Number and title of this funding opportunity
The letter of intent should be sent to:
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed, with the following exceptions or additional requirements:
The Research Strategy must consist of the following subsections with the indicated page limits:
- Overall Research Section: 30 pages
- Research management plan: 6 pages
- Individual common disease Projects (1-3 required); 6 pages each
Instructions for Application Submission
The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.
All instructions in the SF424 (R&R) Application Guide must be followed.
SF424(R&R) Project/Performance Site Locations
All instructions in the SF424 (R&R) Application Guide must be followed.
SF424(R&R) Other Project Information
All instructions in the SF424 (R&R) Application Guide must be followed.
Facilities and Other Resources. In addition to general information about resources available for the proposed work, applicants should include specific discussion of additional resources available for individula Project plans that could increase the the chances of success of the program. These could include ongoing or matching genomic studies or resources.
SF424(R&R) Senior/Key Person Profile
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
Applicants may propose a single "Pilot Collaboration" of up to $200,000 total costs in the first year. Applicants wishing to pursue "Pilot Collaborations" in the second through fourth years include the budget for those funds. In the budget justification text, please state that the FOA suggests that this amount be included as a placeholder for Years 2-4.
This section should should indicate the approximate percentage of effort--as a proportion of the total request---that key management staff will devote to management tasks as part of the Management plan explicitly, in addition to any other effort on the grant.
The PD/PI is required to devote at least 15% effort (1.8 mos) to this effort.
Project plans should not receive a separate budget. However, the budget section should indicate the approximate overall total cost of each prposed Project plan.
All three project plans together should occupy at most ~40% of overall center capapcity over all four years reserving ~60% for projects to be chosen later. However, the Projects should at least occupy full capacity for the initial year.
R&R Subaward Budget
All instructions in the SF424 (R&R) Application Guide must be followed.
PHS 398 Cover Page Supplement
All instructions in the SF424 (R&R) Application Guide must be followed.
PHS 398 Research Plan
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
Research Strategy: The Research Strategy should consist of the following subsections, uploaded as a single pdf attachment.
A. Overall Research section: Applicants should follow the general format of the form SF424 Application Guide (i.e., Significance, Innovation, Approach, Preliminary studies) while addressing all the scientific and foundational objectives described in the Research Objectives section above, including discussions about what will be learned about rare variation underlying common complex disease, As discussed above, the applicant should provide a working definition of "comprehensiveness" , considering and balancing the scientific and practical issues, and should make it clear how comprehensiveness will be approached or maximized in the proposed work, as a stand-alone proposal and/or in combination with other existing or ongoing efforts. The applicant should indicate how the proposed work will contribute to achieving comprehensiveness in the context of the overall program.
This section should also include any proposed "Pilot Collaboration" for the initial year (this must be a collaboration outside the grantee department and preferably institution). "Pilot Collaborations" should outline the aim of the collaboration, what will be done, describe why it is significant, how it will achieve the goal of extending comprehensiveness e.g., towards functional characterization of variants, what the potential will be for follow-up should the Pilot Collaboration be fruitful, and how the Pilot Collaboration will have the effect of disseminating the results of one or more Projects and/or the work within the CCDG.
This section should also include all details about the data generation and analysis pipeline, and improvements thereto. Applications should address cost efficiency, adaptability and flexibility of genome sequencing pipelines, including use or adoption of a mix of technologies and applications, as appropriate to efficiently address the scientific aims, while maintianing or driving the state-of-the-art in genome sequencing. Part of the mix may include outsourcing of data generation.
This section should discuss certain technical details that will enable data dissemination and sharing. It should include details about technical capabilities and IT infrastructure in place for the mechanics of data deposition, including its integration with the production pipeline and limits on sharing data with multiple repositories.
Within the Overall section, applicants must report genome sequencing costs. This is not the same as the budget request. Reporting costs will allow evaluation of whether the proposed activity is capable of producing data as efficiently as possible, and also the potential for achieving reduced costs over time. Retrospective costs should be reported for the most recent quarter or three-month (minimum) period. Projected costs should be presented for the entirey of the award period and should include an explanation of how any reductions would be achieved, including discussion of adoption of new sequencing platforms.
Applicants should report costs in a way that is consistent with current NHGRI cost tracking (see Section I, Background on genome sequencing)riefly, both proposed and past data production costs should be reported both as cost per Mb, and cost per whole genome (30X coverage short read, or equivalent); and cost per whole exome (stating associated coverage parameters). Data production costs must include:
- Labor, administration, management, utilities, reagents, and consumables
- Sequencing instruments and other large equipment (amortized over three years)
- Informatics activities directly related to sequence production (e.g., laboratory information management systems and initial data processing)
- Submission of data to a public database
- Indirect Costs (http://oamp.od.nih.gov/dfas/faq/indirect-costs#difference) as they relate to the above items
In addition to genome sequencing costs, applicants are asked to report estimated costs of analysis on a per genome and per exome basis, for costs costs not included in data production. This includes the costs of any automated analyses (including single-nucleotide variant calling), but not manual analyses (i.e., non-automated structural variant calling, or association tests, etc.). These estimates should include associated data storage costs, labor, administration, management, and indirect costs.
Applicants should also concisely indicate their metrics of sequence quality along with the cost per genome and the cost per exome (e.g., in terms of coverage).
Where the application indicates how future production and analysis costs will be reduced, it should do so by reference to the cost and quality reporting elements described above so that reviewers can understand how costs will be reduced, and will have an overall understanding of how the budget requested relates to the proposed work.
This section should not address objectives detailed in the other subsections described below, except as needed to explain any integration between activities.
In sum, the Overall section should:
- Propose an overall rationale and approach to characterizing and understanding the role of rare variation in common disease;
- Explain how common disease rare variant discovery and characterization will be accomplished, with consideration of optimizing "comprehensiveness" as discussed above, and with reference both to specific common diseases and to the general problem of characterizing common disease architecture both to inform how to understand the genomic basis for all common disorders, and more broadly to gain insight into the biology of disease;
- Propose original and significant study designs, approaches, and analyses that will increase the chances of achieving comprehensiveness for individual disease studies and for the entire program;
- Describe how the proposed work will lead to a significant, qualitative gain in scientific understanding, including overall project designs that will be informative even in the case of a negative result (e.g., no or very few further variants found; conversely, no convergence or objective end-point despite extensive sampling and sequencing);
- Propose a flexible, high quality state of the art genome sequencing and analysis pipeline of sufficient scale to match the objectives of the FOA (i.e., that could undertake at least a significant portion of the objectives, and that is capable of undertaking multiple different Projects over the entire award period), that will continue to stay at the forefront and drive the state-of-the-art of genome sequencing and analysis of common disease. This includes both sequence production and development of computational analysis pipelines;
- Describe specific "foundational" outcomes (e.g., resources, new analysis capabilities, tools etc.) as outlined above that will result from the work;
- Describe, for context, how studies have the potential to be extended beyond identification of associated rare variants; propose limited analyses that extend beyond variant discovery and association with common disease, e.g., through computational analyses, and/or if appropriate development of other (e.g. RNA) high throughput datasets that can be produced on genome sequencing platforms;
- Optionally, propose a one-year "Pilot Collaboration" that begins to demonstrate how the funded studies could be extended towards functional characterization of variation, and that also serves the objective of disseminating results;
B. Research Management Plan section: this section should describe a management plan commensurate with the complexity of this effort, including internal reporting relationships and mechanisms for reporting progress to NHGRI (see Terms and Conditions, below) and the decision-making process. This section should also describe management of the sequencing pipeline; coordination of key aspects of the effort (e.g., production with specific Projects and downstream analyses). This section should discuss initiation and coordination of projects in collaboration within the research network, the community, and ability to track and report on multiple projects from sample acquisition through completion of analysis. This section should aslo describe general features of how projects will be initiated in collaboration with the community, and any general structures or resources in place for enhancing collaborations.
The management plan should discuss past experiences in working in large collaborative data production projects of a degree of complexity similar to what is being requested in this FOA.
The Management plan should also include discussion of additional resources that can be used to maximize the chances for success in attaining the Objectives of this program (although those may be discussed in relation to specific Projects).
C. Project plan (up to three): Each Project plan should address aspecific common disease project that will be undertaken over at least the initial year of the award, and should be sufficient to occupy center cpapcity for the initial year. . The Project plan should outline the significance in terms of both the importance of the disease and the Objectives of this FOA (e.g., comprehensiveness, representation across multiple disease architectures). The Project plan should discuss sample sets that are adequately consented for data release and use according to NIH policy (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-14-124.html). The Project plan should discuss how samples have been adequately phenotyped, and how they will be available to the investigator so that work can begin on funding. The ideal samples would also be amenable for use in extended studies (see "comprehensiveness", above). (NHGRI acknowledges that available sample sets may not be ideal for all purposes.)
The Project plan should discuss power and design considerations specific to the project (general considerations should be in the Overall section), describe work already done and ongoing, describe the communities that will make use of the data, describe collaborations and considerations regarding making the data available specific to that community that are not generally described in the Resource Sharing Plan. The Project plan section should briefly indicate the amount and proportion of sequencing capacity that will be required (i.e., numberof genomes, number of Mb). . For each specific Project, applicants should describe how any other related ongoing efforts or projects could synergize or be combined with the proposed project towards the goals of the FOA, for example by afofrding improved statistical power.
Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:
- All applications submitted for the January 25, 2015, due date or after are expected to comply with the NIH Genomic Data Sharing Policy as detailed in NOT-OD-14-111, as applicable.
- All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
The Resource Sharing Plan is expected also to include:
- How sequence data (including genomic, RNA, and other high throughput data) variant, assembly and other data will be shared in a manner consistent with NIH policy.
- It is possible that specific Projects, especially those that are done in collaboration with another NIH Institute, will require that sequence (or other data) be deposited in a disease-specific repository, and also in dbGaP or similar general NIH repository. This section should discuss how this would be managed if this situation arises.
- How research tools (including informatics analysis or data processing tools) and new methods developed under this award will be made available.
Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
Planned Enrollment Report
When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide.
PHS 398 Cumulative Inclusion Enrollment Report
When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.
3. Submission Dates and Times
Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission.
Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date. If a Changed/Corrected application is submitted after the deadline, the application will be considered late.
Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.
Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.
4. Intergovernmental Review (E.O. 12372)
This initiative is not subject to intergovernmental review.
All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Pre-award costs are allowable only as described in the NIH Grants Policy Statement.
6. Other Submission Requirements and Information
Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.
Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.
For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues.
All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.
The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.
See more tips for avoiding common errors.
Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.
In order to expedite review, applicants are requested to notify the NHGRI Referral Office by email at firstname.lastname@example.org when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.
Post Submission Materials
Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030. In addition to the topics described therein, applicants may submit updates about new publications, updates on the status of Project plans that have to do with availabiliuty of samples, availability of additional resources that are critical for the proposed work. These materials may also incude brief updates about new sequencing technologies that would be used that could significantly change data production. The total length of the update materials may not exceed three pages. The Scientific Review Officer will set deadlines for receipt of post-submission materials.
Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.
For this particular announcement, note the following: All subsections of the Research Strategy (Overall, Management, and Projects) will be reviewed and scored as a whole. However, the "Pilot Collaboration" outlines will not be included in the score.
Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).
Scored Review Criteria
Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.
Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?
Does the proposed research plan represent a comprehensive rare variant study or studies that will significantly inform basic questions about the architecture of common diseases? Are the questions being asked or approaches being developed by the applicant of high relevance for genomics in particular and biomedical science in general?
Is the proposed work likely to result in foundational outcomes, e.g resources, datasts, methodolgies infromatics tools, that will be of high value to the communities studying common disease and the wider community?
Is there a high likelihood that the proposed center can produce high-quality genomic (or other) sequence and analyses in the context of a common disease study, based on the applicant’s past experience and the proposed future plans for generating high quality data and other kinds of large-scale sequencing products as discussed in this FOA?
Is there a high likelihood that the applicants can accomplish this work at and beyond current state-of-the-art levels of throughput, data quality, and cost? Is there a high likelihood that the center will make significant contributions to the state-of-the-art in sequencing, especially as applied to discovering the role of rare variants in common disease, including new applications and/or project designs for the kinds of project requested herein?
Does the research plan considered as a whole take good advantage of the current state-of-the-art in high throughput sequencing? Does it have good potential to drive the state-of-the-art e.g. in adaptation of technology or project design?
Is there a high likelihood that the center will provide significant leadership for sequence-based biology?
Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?Do the PIs/PDs have successful experience in leading large collaborative projects? In leading large data production efforts?
Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?
Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?
Is the issue of "comprehensiveness" adequately considered in the approach? Does the application address the overall goals of "comprehensiveness", with regard to e.g., statistical power to detect disease-associated variants; exploration of coding vs. noncoding sequence, populations examined, exploration of diverse project designs, and exploration of a range of disease architectures? Does it strike a good balance between the scientific and practical considerations in defining such studies?
Is the approach likely to lead to qualitative conclusions beyond just additional disease-associated variants) that are significant for understanding common disease architecture and biology? Will it do so even if the results of a particular study are negative?
Is the overall approach likely to be flexible enough to successfully accommodate multiple different projects, potentially with diffferent designs or phenotypes, over time, including ones identified later in the course of the award period by NHGRI?
Will the approach yield important lessons about how to design common disease rare variant studies, even if the results are negative (e.g., in the event that few additional contributing variants are found, or in the event that there is no convergence or evident stopping point for discovery of variants underlying specific diseases)?
Is it likely that the proposed projects have high potential to be extended beyond genome sequencing?
If the applicant proposes high-throughput data generation modalities other than genomic sequencing (including genotyping, RNA sequencing, using sequencing platforms to assess DNA methylation), or disease variant discovery in well-chosen non-human model organisms, or phenotypes that are not strictly disease phenotypes, are they deployed in a way that is creative, well-delimited and well-integrated with or complementary to other components of the research plan?
Are analysis plans and capabilities well-described and likely to be successful in all stages of data and variant analysis?
Is the informatics infrastructure described adequate to support proposed analyses and data deposition requirements, including collaborations?
Are planned technical or other improvements in data production, informatics, and analysis capabilities well-justified (e.g., in terms of the need to improve capabilities for data processing, analysis, etc. in order to increase chances of success in meeting the Objectives) and integrated with each other?
Are the research plan and track record of the applicant sufficient to give confidence that ambitious goals can be accomplished?
Is the management plan well-described and commensurate with the level of complexity required by this FOA? Is it likely to successfully manage and integrate multiple individual project plans, (including required community collaborations) with sequence production and analysis?
If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?
Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?
Is institutional or other infrastructure adequate? This includes not just space and facilities, but information technology infrastructure and support, including data storage capability.
Are there additional resources for either individual Projects or the effort as a whole that would be available?
Additional Review Criteria
As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.
Does the management plan clearly describe how the effort will be managed to maximize the likelihood for success, considering the size and complexity of a CCDG, and the need for managing multiple simultaneous projects and collaborations? Are there clearly described roles and reporting relationships for key personnel? Are there sound plans for how to manage multiple projects and for participation in collaborations? Is the institutional or other infrastructure---including IT resources-- conducive to a sucessful outcome?
Do the investigators have a successful track record managing large collaborative data generation projects of a degree of complexity similar to what is being requested in this FOA?
Are technical plans and capabilities for data deposition and sharing data with collaborators adequate? Are they flexible to accommodate multiple collaborations (any of which, for example, may require deposition to or other collaboration with a community data portal)?
Is there a plan for identifying other resources that could leverage the funds provided by this initiative?
Are the proposed Projects significant? Within the limits of the resources that would be made available, will the proposed projects expand the range of disease architectures under investigation, or will they complete studies that are not yet comprehensive? Is the design meritorious and likely to be successful in comprehensively identifying variants underlying disease (e.g., power or quality of phenotyping)? Are the samples appropriate/adequate, including choice of population, consent, availability, quality of phenotyping? Are there innovative design elements, for example those that are likely to improve comprehensiveness and/or efficiency, or test hypotheses about designs that are appropriate to specific disease architectures?
Are collaborations with relevant disease-research communities well-described and are they likely to help disseminate or result in extension or use of the basic findings? Will the project leverage other resources, for example through the availability of other funding or other resources that will increase the likelihood of project success?
Do the proposed Projects, considered as a set, successfully balance the various aspects of "comprehensiveness", including exploration of coding vs. noncoding sequence, exploring different architectures and designs, populations---especially those that have been under-represented in this type of study---and practical issues (e.g., cost vs. power or interpretability)?
Protections for Human Subjects
For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.
For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.
Inclusion of Women, Minorities, and Children
When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.
The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.
Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.
Additional Review Considerations
As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.
Is the Pilot Collaboration significant? Will it effectively extend the proposed work (e.g. by exploring function of variants implicated in phenotype?) Is the approach novel? Will the pilot study have a high potential to provide enough data or other information to lead to an independent project? Is the pilot likely to have the effect of disseminating the Center's results? Although the Pilot Collaborations should not be considered part of the overall score, NHGRI seeks reviewer input on whether proposed Pilot Collaborations are of high quality.
Applications from Foreign Organizations
Select Agent Research
Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).
Resource Sharing Plans
Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genomic Wide Association Studies (GWAS) /Genomic Data Sharing Plan.
Budget and Period of Support
Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.
2. Review and Selection Process
Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the National Human Genome Research Institute in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.
As part of the scientific peer review, all applications:
- May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
- Will receive a written critique.
Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.
Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Council for Human Genome Research. The following will be considered in making funding decisions:
- Scientific and technical merit of the proposed project as determined by scientific peer review.
- Availability of funds.
- Relevance of the proposed project to program priorities. This includes:
- Program balance, including the desire to ensure that study of a diversity of disease architectures, designs, populations--- including those that are currently under-represented in such studies--- is achieved within the overall funding that will be provided through this FOA.
- Flexibility of the proposed effort, in the context of the overall program, to undertake multiple collaborative projects over time, and to have the potential to expand to undertake new opportunities that may arise.
- The quality of existing collaborations on common disease projects.
- The ability to work effectively in large collaborative efforts or research consortia.
- The resources available that could leverage NHGRI funds towards the attainment of the Objectives of this FOA.
- Compliance with data and resource sharing policies.
3. Anticipated Announcement and Award Dates
After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons.
Information regarding the disposition of applications is available in the NIH Grants Policy Statement.
1. Award Notices
If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.
A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.
Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.
Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.
2. Administrative and National Policy Requirements
All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.
Cooperative Agreement Terms and Conditions of Award
If this FOA is not a cooperative agreement, make no changes to this section. If it IS a cooperative agreement, fill out the template "Cooperative Agreement Terms and Conditions of Award" as appropriate. THEN, copy and paste all the text from that template into this section, replacing "Not Applicable" (below) with your text.
The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.
The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.
The PD(s)/PI(s) will have the primary responsibility for:
Awardees are responsible for defining, within the context of this FOA, objectives and approaches, and for planning, conducting, analyzing, and publishing results, interpretations, and conclusions of their studies.
The awardees will agree to accept close coordination, cooperation, and participation of NHGRI staff in those aspects of scientific and technical management of the project as described under "NIH Staff Responsibilities."
P.D(s)./P.I(s). of a Center for Common Disease Genomics will:
- Determine experimental approaches, design protocols, set project milestones and conduct experiments;
- Provide goals for throughput, quality, cost and specific project completion to the NHGRI as requested (usually at the outset of the award and annually thereafter, but also at other times as requested by NHGRI program staff);
- Ensure that the genomic sequence produced meets the quality standards and costs agreed upon at the time of award or any improved quality standards and costs negotiated during the award period;
- Ensure that the sequence data (reads, variants, assemblies) are deposited in the appropriate public database (e.g., GenBank or other, as specified by NHGRI program staff), that resources developed as part of this project are made publicly available according to NHGRI policies, and that results are published in a timely manner;
- Adhere to the NHGRI policies regarding intellectual property, data release and other policies that might be established during the course of this activity (see http://gds.nih.gov/03policy2.html);
- Integrate with the NHGRI’s process for selecting new Projects. Work cooperatively and constructively with Program Staff to carry out projects identified by NHGRI as meeting the goals of the program.
- Work productively with program staff from other NIH institutes who may be providing co-funding for projects. In some cases, NHGRI may ask representatives from other NIH institutes to participate in Steering Committee activities.
- Submit data for quality assessment in any manner specified by the Steering Committee or the External Scientific Advisors to the program;
- Submit quarterly progress updates in a standard format, as agreed upon by the Steering Committee and the External Scientific Advisors;
- Accept and implement any other common guidelines and procedures developed for the NHGRI large-scale sequencing program and approved by the Steering Committee and the External Scientific Advisors;
- Accept and participate in the cooperative nature of the NHGRI Genome Sequencing Research Network composed of awardees to this FOA and other components of the NHGRI Genome Sequencing Program, including:
- Within the CCDG, direct collaborations between awardees on large projects with shared phenotypes, which may include collaborations initiated by NHGRI through the new Project selection measures described in this RFA, and collaborators funded by other NIH Institutes and Centers on projects that may require participation of multiple communities and funders
- With the Centers for Mendelian Genomics that will be funded as part of the overall program
- With any Coordinating Center or analysis projects that NHGRI plans to solicit as part of the overall program, including being responsive to Coordinating Center requests
- Where opportunities are identified, participate in collaborations with other NHGRI research networks.
- Coordinate and collaborate with other U.S. and international groups engaged in large-scale genomic sequencing or other large projects;
- Inform the Program Director of all major interactions of members of the Steering Committee;
- Attend Steering Committee meetings, attend annual program meetings.
Awardees will retain custody of and primary rights to their data developed under the award, subject to current Government policies regarding rights of access.
NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below, during the conduct of this activity, in order to provide technical assistance, advice and facilitate coordination. However, the role of NHGRI will be to facilitate and not to direct the activities. It is anticipated that decisions in all activities will be reached by consensus of the Genome Sequencing Research Network and that NHGRI staff will participate fully in this process.
One NHGRI Project Scientist shall participate as a member of the Steering Committee and will have one vote.
The Project Scientist will:
- Participate (with the other Steering Committee members) in the group process of setting research priorities, deciding optimal research approaches and protocol designs including for new Projects introduced after awards are funded, and contributing to the adjustment of research protocols or approaches as warranted. The Project Scientist will assist and facilitate the group process and not direct it;
- Negotiate throughput, quality, cost goals, and sequencing target selection with the awardees as necessary;
- Manage the processes for selecting new Projects as described in this RFA; final decisions about new Projects will be made by the Director, NHGRI in consultation with the Project Scientist, with advice from one or more of: the External Scientific Panel, an X01 review process; the National Advisory Council on Human Genome Research.
- Serve as a liaison between the awardees and the External Scientific Panel, the National Advisory Council for Human Genome Research, and the larger scientific community in helping the awardee(s) select and coordinate new Projects;
- Coordinate the efforts of the awardees with other awardees under this FOA and related NHGRI programs; with other NIH institutes and their research communities, and with the international sequencing community;
- Attend all Steering Committee meetings as a voting member and assist in developing operating guidelines, quality control procedures, and consistent policies for dealing with recurrent situations that require coordinated action;
- Periodically report progress to the Director, NHGRI;
- Lend relevant expertise and overall knowledge of NHGRI-sponsored research to facilitate the selection of scientists not affiliated with the awardee institutions who are to serve on the External Scientific Panel; serve as liaison between the Steering Committee and the External Scientific Panel;
- Serve on subcommittees of the Steering Committee and the External Scientific Panel, as appropriate;
- Provide advice on the management and technical performance of the investigation;
- Assist in promoting the availability of the genome sequence and related resources developed in the course of this project to the scientific community at large;
- Participate in data analyses, interpretations, and where warranted, co-authorship of the publication of results of studies conducted through the Genome Sequencing Research Network;
- Assist awardees in the development, if needed, of policies for dealing with situations that require coordinated action;
- In cases where NHGRI decides to withhold funds for programmatic (rather than performance) reasons, will serve as primary liaison between the External Scientific Panel, and the Director, NHGRI, regarding how those funds should be awarded.
- Retain the option to recommend, with the advice of the External Scientific Panel, the withholding or reduction of support from any cooperative agreement that substantially fails to achieve its goals according to the milestones agreed to at the time of award, fails to maintain state-of-the-art capabilities, or fails to comply with the Terms and Conditions of the award.
Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. The assigned program director may also serve as the NIH Project Scientist.
NHGRI plans to reserve a proportion (30-50%) of funds at the beginning of each grant year, and distribute it half way through the grant year based on progress and other factors that significantly increase the chances that the program objectives will be achieved. The primary factors that will be used to evaluate the distribution will include achievement of milestones, identification of resources that will make a project more comprehensive or allow additional projects to be completed, as long as those projects contribute to the overall objectives detailed in this RFA. The External Scientific Panel will advise NHGRI on the development of criteria, and the distribution of funds.
Areas of Joint Responsibility include:
Participation in the Steering Committee. A Steering Committee will serve as the main governing board of the Research Network. The Steering Committee membership will include the NHGRI Project Scientist(s) and the P.I. of each awarded cooperative agreement. In some cases where co-funding has been provided, NHGRI may include program staff from other NIH institutes. The Steering Committee Chair will not be an NIH staff member. Additional members may be added by action of the Steering Committee. Other government staff may attend the Steering Committee meetings, if their expertise is required for specific discussions. Because the Research Network will include investigators funded by this FOA and other FOA's for the NHGRI Genome Sequencing Program, it is possible that NHGRI staff will create appropriate subcommittees to handle interests that may be specific to a set of awardees under a specific FOA.
The Steering Committee will:
- Discuss progress in meeting the objectives of the program;
- Develop recommendations for uniform procedures and policies necessary to meet the goals of the Research Network, for example for data quality measures and assessment, conventions for data deposition, or measuring costs and throughput. Develop recommendations about the types of data analyses to be done and how best to achieve them. Adoption of procedures and policies developed by the Steering Committee will require concurrence by the External Scientific Panel;
- Serve as a venue for coordination on the improvement of the ability to carry out comprehensive common disease rare variant studies.
- Serve as a venue for coordination on improvements in genomic sequencing, for example by disseminating best practices and collectively evaluating new procedures, resources, and technologies.
- Schedule the time for, and prepare concise summaries of, the Steering Committee meetings, which will be delivered to members of the group within 30 days after each meeting.
- Each full member (limited to one person per awarded center, in the case of multiple PI’s per center) will have one vote except NHGRI Project Scientist(s), who will have one collective vote.
- Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.
- Another area of joint responsibility is that NHGRI and the grantees will work with and provide information to an External Scientific Panel (ESP). The ESP will be responsible for reviewing and evaluating the progress of the members of the Genome Sequencing Research Network toward meeting their individual and collective goals. The ESP will provide recommendations to the Director, NHGRI, about continued support of the components of the Genome Sequencing Research Network. If funds are withheld by NHGRI for programmatic reasons, rather than performance reasons, the ESP will provide advice to NHGRI regarding the distribution of those funds. The Advisory Panel is composed of six to ten senior scientists with relevant expertise who are not P.I.s of a cooperative agreement involved in the Genome Sequencing Research Network. The membership of the Scientific Advisory Panel may be enlarged permanently, or on an ad hoc basis, as needed.
- The ESP will meet at least once a year. During part of this meeting, there will be a joint meeting with the Steering Committee to allow the Scientific Advisory Panel members to interact directly with the awardees. The ESP will make recommendations regarding progress of the Genome Sequencing Research Network and present advice about changes, if any, which may be necessary in the Genome Sequencing Research Network program to the Director, NHGRI.
Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought, at the request of an awardee, to Dispute Resolution. A Dispute Resolution Panel will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in a case where only one awardee has the disagreement, the first member may be chosen by the individual awardee. These special arbitration procedures in no way affect the awardee's right to appeal an adverse action in accordance with PHS regulations at 42 CFR Part 50, Subpart D, and HHS regulations at 45 CFR Part 16.
A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.
The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.
We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.
Application Submission Contacts
eRA Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
Finding Help Online: https://grants.nih.gov/support/index.html
GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
National Human Genome Research Institute (NHGRI)
Peer Review Contact(s)
National Human Genome Research Institute (NHGRI)
Financial/Grants Management Contact(s)
National Human Genome Research Institute (NHGRI)
Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Authority and Regulations
Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.