National Institutes of Health (NIH)
National Human Genome Research Institute (NHGRI)
Funding Opportunity Title
Population Architecture Using Genomics and Epidemiology (PAGE), Phase II � Coordinating Center (U01)
U01 Research Project � Cooperative Agreements
Funding Opportunity Announcement (FOA) Number
Companion Funding Opportunity
Catalog of Federal Domestic Assistance (CFDA) Number(s)
Funding Opportunity Purpose
The purpose of this funding opportunity is to provide centralized support and coordination for the studies and investigators funded under the Population Architecture Using Genomics and Epidemiology (PAGE) program (RFA-HG-12-010), who will sample and assess genomic variation from well-phenotyped individuals of non-European (EA) ancestry and disseminate the resulting data to form a population resource that will expand understanding of ancestral differences in genomic disease associations. This four-year program will extend the initial experience of PAGE I to add large-scale, dense assays of common and rare coding and/or potentially functional genomic variation in a large number of non-EA ancestry participants with existing and extensive phenotype information.
June 20, 2012
Open Date (Earliest Submission Date)
September 18, 2012
Letter of Intent Due Date
September 18, 2012
Application Due Date(s)
October 18, 2012, by 5:00 PM local time of applicant organization.
AIDS Application Due Date(s)
Scientific Merit Review
Advisory Council Review
Earliest Start Date(s)
October 19, 2012
Due Dates for E.O. 12372
Required Application Instructions
It is critical that applicants follow the instructions in the SF 424 (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.
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 purpose of this funding opportunity is to provide centralized support and coordination for the studies and investigators funded under the Population Architecture Using Genomics and Epidemiology (PAGE) program (RFA-HG-12-010), who will sample and assess genomic variation from well-phenotyped individuals of diverse ancestry, particularly those of non-European ancestry (EA), and disseminate the resulting data to expand understanding of ancestral differences in SNP-disease associations observed in PAGE Phase I and similar studies. This four-year program will extend the initial experience of PAGE I to add large-scale, dense assays of common and rare coding and/or potentially functional genomic variation in a large number of diverse ancestry participants, particularly groups with disproportionate disease burdens, and with existing and extensive phenotype information. For the purposes of this FOA, �assess genomic variation� means using the most comprehensive and cost-effective technology to capture the majority of inter-individual variation; currently the �exome chip� but likely to evolve over the four-year course of this FOA. Collections of �well-phenotyped individuals� may be cross-sectional, if extensive, or, preferably, prospective and longitudinal. �Non-EA� and �ancestrally diverse� populations refer to individuals whose ancestral (e.g., grandparents�) continent of origin lies outside Europe. �Potentially functional variation� means coding or non-coding variants that influence genomic function and are related, or suspected of being related, to human diseases.
The goals of this program are to collaboratively utilize existing population-based cohorts to:� 1) identify disease-associated genomic regions where between-population differences may be attributable to differences in allele frequency or LD structure; 2) build a population resource of non-EA individuals whose comprehensive genotype and phenotype data would serve as a reference population for the scientific community; and 3) explore the associations of DNA sequence variation with a broad range of phenotypes, including conditions with disproportionate disease burdens in persons of non-EA ancestry.��
This funding opportunity will provide support for activities that will support the PAGE II Consortium and its Working Groups.� The PAGE II CC will have primary responsibility for organizing and coordinating cross-study activities, as described further below.
To ensure that the maximal scientific benefit is derived from this significant public investment, this funding opportunity aims to support widespread sharing of the resulting data with the broad scientific community for research use, through community resource databases such as dbGaP (http://www.ncbi.nlm.nih.gov/gap) or other databases to be developed within or outside this project.
PAGE Phase I is an ongoing, five-year cooperative agreement funded to utilize existing population-based cohort studies and clinical trials to: 1) determine the population-based profile, or �epidemiologic architecture,� of potentially causal variants, including prevalence in racial and ethnic subgroups of relevance to the U.S. population and magnitude of disease risk and associations with other health characteristics; 2) identify modifiers of gene-trait associations, particularly lifestyle factors or medication use; and 3) identify potential clues to the biological basis of an association by studying the relationship of the robustly associated variants to phenotypic characteristics such as laboratory measures or imaging findings.� In July, 2008, NHGRI funded 4 grants in response to RFA-HG-07-014, �Epidemiologic Investigation of Putative Causal Genetic Variants� (https://grants.nih.gov/grants/guide/rfa-files/RFA-HG-07-014.html) and 1 grant in response to RFA-HG-07-015, �Epidemiologic Investigation of Putative Causal Genetic Variants � Coordinating Center�.� Collectively, PAGE analyses have included more than 100,000 participants, representing individuals of European ancestry as well as individuals of African American, Hispanic/Latino, Asian, Native Hawaiian, and American Indian ancestry.� Among the approximately 70,000 non-EA PAGE participants analyzed during the later project years, 49% are African American, 31% Hispanic/Latino, 18% Asian, and 2% Native Hawaiian. PAGE I analyses leveraged the considerable breadth and depth of phenotypes from these cohorts to compare cross-population allele frequencies, relative risks, and distribution of phenotypes associated with particular variants and their environmental modifiers among populations of European and non-EA descent. This work was accomplished through the formation of many Working Groups, convened to harmonize phenotypes, conduct consortium-wide meta-analyses and write manuscripts, and provide consistent guidance across the consortium with regards to statistical analyses, ethnicity/ancestry analysis, publications, and implications for data display and dissemination. Key findings from PAGE I include characterization across multiple ancestral groups of lipid and metabolic traits, stroke, coronary heart disease, endometrial cancer, and type 2 diabetes.� In addition to conducting carefully harmonized and a priori analyses of specific traits, PAGE I analyzed and deposited association data across nearly all phenotypes, yielding data suitable for preliminary, highly exploratory phenome-wide association studies (PheWAS).�
As the limitations of characterizing a genome-wide association study (GWAS) locus in diverse ancestry populations using a single variant became evident, PAGE undertook a pilot study in 2009 to test the feasibility and value of expanding genotyping to denser fine mapping around many GWAS loci.� This pilot study, made possible by the American Recovery and Reinvestment Act (ARRA), genotyped approximately 5,000 African Americans using the Metabochip, a dense genotyping array of ~200K SNPs, including ancestry-specific fine mapping variants, for a range of metabolic and cardiovascular traits. The resulting pilot data demonstrated a number of GWAS associations that do not generalize to African American populations, demonstrating the importance of dissecting GWAS signals in an ethnic-specific way. Taking advantage of increased cost-efficiencies in genotyping arrays and the need for dense genotyping data from diverse ancestry groups, in the latter years of the project period PAGE is generating and analyzing Metabochip data on approximately 70,000 participants of African American, Hispanic/Latino, Asian, and Native Hawaiian descent. Summaries of the PAGE Steering Committee (SC) and External Scientific Panel (ESP) discussions which led to this shift in genotyping are available at https://pagestudy.org/index.php/public-documents.�
PAGE II seeks to expand understanding gained during PAGE I and similar studies of how ancestry-specific differences in allele frequencies and LD may explain differences in risks of common traits and conditions. Recent studies have identified rare genetic variants that are likely to contribute to common diseases and traits and observed that rare variants likely to be functional, such as those in coding and regulatory regions, tend to be population-specific.� PAGE II is expected to start with the most comprehensive and cost-effective technologies currently available, such as the next generation of high density genotyping arrays (e.g., exome chip) to continue its emphasis on characterizing population-level disease risks in non-EA individuals. As sequencing technologies advance in efficiency and decline in cost, PAGE II may adopt more advanced approaches as was done in PAGE I.
Scientific Knowledge to be Achieved
This funding opportunity and the related RFA-HG-12-010, �Population Architecture Using Genomics and Epidemiology (PAGE), Phase II � Study Investigators�, will provide detailed, population-based information on genomic variants robustly associated with or strongly suspected of influencing complex diseases and traits. It will do so in a rapid and cost-effective manner by assaying these variants in representative population samples already well-characterized for a number of phenotypic traits and exposure variables. The individual-level genotype and phenotype data and resulting descriptive data will be provided to an NIH-designated data repository for dissemination to the scientific community.
Objectives of this Research Program
This FOA will provide centralized support and coordination for the studies and investigators funded under the Population Architecture Using Genomics and Epidemiology (PAGE) program (RFA-HG-12-010), who will sample and assess genomic variation from well-phenotyped individuals of diverse ancestry, particularly those of non-European ancestry (EA), to expand understanding of ancestral differences in SNP-disease associations observed in PAGE Phase I. Applicants should describe their plans for coordinating, facilitating and supporting the activities of this program in collaboration with the Study Investigators and NHGRI. These activities will likely include, but are not limited to:
Investigative groups will be responsible for study design, genetic assays, analysis and data submission of their individual studies to the CC and to dbGaP.� The CC will be responsible for providing support and assistance to accomplish the goals of the program.� Applicants should describe their experience in working as part of a research consortium or other collaborative activities that included both laboratory and clinical/epidemiologic partners.� Together with the Study Investigator groups, the CC will work to coordinate genotyping and analysis of disease-associated genomic regions where between-population differences may be attributable to differences in allele frequency and/or LD structure.� To maximize the numbers of diverse and well-phenotyped participants in PAGE II (at least ~10,000 participants per site over the project period), cost-effective high-density SNP arrays will be the primary source of genotyping technology. Whereas PAGE I focused on characterizing findings from GWAS, PAGE II will focus on extending regions of interest to findings from sequencing studies, particularly those in exonic or potentially functional regions of the genome.� Depending on the prevailing content of exonic-focused genotyping arrays at the time PAGE II genotyping is underway, efforts to augment this content with genetic variation representative of diverse ancestry populations using additional genomic assays may be a key focus of PAGE II. The final choice of genotyping array(s) or technology will be discussed and agreed upon by the PAGE SC in conjunction with the NHGRI, and may evolve over the project period.� As in PAGE I, genotyping will likely revolve around approximately yearly batches to facilitate cross-study analyses throughout the project period. Investigators should describe the expertise that makes them well qualified to address the challenges and opportunities inherent to assessing and implementing rapidly changing technology to accomplish the goals of PAGE II. These discussions will provide valuable guidance to the studies participating in this program and to population studies in general.
Once approaches for genetic investigations are generally agreed upon, subsequent investigation within the consortium supported by this program might include: 1) prioritizing appropriate participants within studies to be assayed and the relevant phenotypic and exposure data to be used in analyses; 2) conducting genotypic and other evolving genomic assays as needed to characterize novel and reported associations; 3) contributing scientific expertise to PAGE-wide phenotype harmonization efforts; 4) contributing individual-level genotype and phenotype data to one or more PAGE-wide datasets for centralized (i.e., consortium-wide) analyses;� 5) analyzing the resulting data in detail, in relation to all or nearly all the relevant phenotypic, covariate/exposure, and population ancestry data available; and 6) inviting collaborations with outside investigators for further functional or translational research. The most rapid possible timeframe for these steps should be proposed, and should continue to accelerate over the course of the program as efficiencies and best practices evolve. The CC is expected to be most actively involved in steps 3-6 above, particularly in developing program-wide approaches to data synthesis and presentation that facilitate collaboration and comparability across participating studies, as well as promoting accessibility and ease of use for investigators outside the program.� The CC may also assist individual investigative groups as needed, and will work with all participating groups to develop the framework for all the steps above.
Applications in response to this FOA should propose approaches to consortium-wide phenotype harmonization efforts and data synthesis and presentation that maximize information on population impact and potential gene function, while minimizing spurious findings and difficulty sifting through the resulting analyses.� Innovative bioinformatic approaches for identifying and displaying potentially important findings should be proposed and applied program-wide, as appropriate, to increase the ease of use of the consortium-wide results.� Sharing of expertise and experience in this and other areas across investigative groups, facilitated and encouraged by the CC and NHGRI, will be a major goal of this collaborative program.
Applications should also propose methods for coordination among investigative groups, analysis within and across participating studies (to be conducted by the investigative groups and/or the CC as appropriate), synthesis of findings, cataloguing the characteristics of participating studies, and invitations to collaborate with participating studies.� Applicants should propose information to be collected from investigative groups to describe their studies, such as source population, eligibility criteria, informed consent and consultation process, breadth and quality of phenotype data, and numbers and demographics of participants currently in the population study or proposed for inclusion, as well as specific provisions of current informed consent and IRB approvals for dissemination of individual-level genotype and phenotype data and any restrictions on research use of the data.�
Applications should describe how this information will be collected from investigative groups, compiled and formatted, and, as needed, provided to databases such as dbGaP, as well as approaches for reaching consensus on program-wide approaches to providing these data.� Although rigid uniformity across all participating studies may be neither feasible nor desirable, common approaches should be pursued to the degree possible to promote efficiency, ease of use, and comparisons across studies.
Investigative groups funded through RFA-HG-12-010 will in general be expected to have the experience and expertise to characterize their studies, and to perform and provide individual-level data in an agreed-upon format. The CC is expected to organize the development of standardized analysis plans and/or data submission templates, as decided upon by the PAGE SC. In some instances, however, investigative groups may need guidance and assistance from the CC in performing these functions.� The CC should be prepared to assist as needed, providing appropriate expertise both for performing analyses and for developing the necessary analytic capabilities within the investigative groups.� The CC will also propose and implement approaches for evaluating quality of the data provided by the investigative groups for submission to dbGaP and similar databases.� Although it is expected that databases such as dbGaP will be the primary vehicle for disseminating information about and from these studies to the scientific community, other approaches may be appropriate and desired.� Development of new tools and databases for providing such information will be supported under this FOA; these tools should be made freely available to the scientific community during the course of this award and provisions proposed for turning their maintenance over to a suitable archive at the end of the grant period.
The CC will also organize and facilitate discussions to arrive at consensus genotyping array(s) or technology and relevant quality control metrics within the consortium. Applicants should describe prior experience with leading or participating in similar activities and proposed approaches to collecting and disseminating this information.� Each Study Investigator applicant to RFA-HG-12-010 will include genotyping costs for his/her proposed research.� Given the importance of minimizing costs and maximizing efficiency, shortly after review NHGRI will compare prevailing costs and timeframes for genotyping proposed at each investigative site to centralized genotyping at large-scale, high throughput facilities. Should NHGRI decide to centralize genotyping, the CC awardee, under guidance from NHGRI, will solicit a subcontractor to perform PAGE-wide genotyping.� Additional funds would be provided for these genotyping activities. Coordinating Center applicants should describe their approach for selecting a centralized genotyping facility to ensure minimal costs and maximal efficiency throughout the course of the project, but should not propose a genotyping facility nor include genotyping costs in the budget at the time of application. Upon request by NHGRI and following peer review, CC applicants should be prepared to propose a budget for genotyping 40,000 samples from investigative groups over the four-year project period, including personnel, supplies, indirect costs, etc.� Applicants should also describe prior experience in collaborating with such facilities.
Pooling of analyses and harmonization of phenotypes across investigative groups are expected to be major components of this program.� A key aim of PAGE II will be to take advantage of the large, ancestrally diverse population samples collectively available throughout the consortium.� Accordingly, SI applicants will propose a set of cross-study analyses that their group would be well suited to lead within PAGE II, recognizing that cross-study analyses, prioritized by the SC, will be done where possible. The PAGE II CC�s role in this process will be to organize phenotype harmonization efforts; synthesize individual-level genotype and phenotype data from each investigative group into one or more PAGE-wide datasets for analytic use, to include data cleaning and QC; and disseminate this centralized dataset to PAGE Investigators and to dbGaP or other data repositories. Sharing of expertise and experience� across investigative groups will be a major goal of this collaborative program, with the intent of better understanding the characteristics and implications of genetic variants that generalize across multiple ancestry groups, and making the resulting findings available and understandable to investigators from a wide range of disciplines.
The CC funded by this FOA will manage the logistics of the program in collaboration with the NIH Program Office, including organizing meetings and teleconferences, distributing materials, recording draft minutes for Program Office review, etc.� Costs for these activities and for three in-person SC meetings per year, one of which will include travel for six ESP members, should be included in the proposed budget.� The CC will also be responsible for obtaining reports and other information from the investigative groups and preparing reports for review by NIH program staff, outside advisors including the ESP, etc.
The CC will work collaboratively with investigative groups and NCBI to provide information on study characteristics and descriptive data for distribution through dbGaP.� The exact boundaries of the activities of the CC, the investigative groups, and NCBI are not possible to predict at this time, and will depend in large degree on the capacities and experience of the investigative groups.� These responsibilities will need to be negotiated once the project is funded and underway, and may change as scientific opportunities present themselves.� Applicants should describe their willingness to be flexible in assuming or relinquishing responsibilities as program needs arise.
Funding will be provided to support methodologic development and lead collaborative activities such as phenotype harmonization, technical assessment or performance evaluation of various assays for genotyping or other technology, and for analyzing, synthesizing, disseminating, and interpreting the resulting data.� No participant recruitment or direct data collection for use in genome-wide studies (such as questionnaires, examinations, or laboratory measures) will be supported by this FOA.
The award funded under this FOA will be a cooperative agreement (see Section VI.2.A. Cooperative Agreement Terms and Conditions of Award). The solicitation: �RFA-HG-12-010, Population Architecture Using Genomics and Epidemiology (PAGE), Phase II � Study Investigators,� will support the investigative groups who will sample and assess genomic variation from well-phenotyped individuals of non-EA ancestry to expand understanding of ancestral differences in disease associations with genomic variants.� Close interaction among awardees and the NIH will be expected to develop appropriate strategies and tools to carry out this program. The awardees will meet as a Steering Committee (SC), which will include the PD(s)/PI(s) from each investigative group, the Coordinating Center (CC), and the NIH Project Scientist, to first examine the phenotypic, covariate, and exposure data available in each participating population study, including the variables collected, methods used, and documentation available. Sample sizes specific for phenotypes of high program-wide priority and for major ancestral groups will be assessed and documented by each awardee across all participating studies. Information on study design, characteristics, and available data will be compiled by each investigative group and provided to the CC for public dissemination in a user-friendly manner. Information on study design, characteristics, available data and quality and quantity of DNA available for PAGE analyses will also be compiled by each investigative group and formatted for public dissemination in a user-friendly manner.
Options for genomic investigations will be discussed by the SC. Once a consensus regarding genotyping platform(s) is reached, the SC will prioritize the highest priority genomic regions and their associated phenotypes, in the context of the overall racial/ethnic distribution, for characterization in the various ancestral groups. Although the primary focus of PAGE II will be to further characterize disease-associated regions, opportunities to use the data to facilitate discovery of novel genomic variants across the allelic frequency spectrum will also be explored.� The SC will also identify strengths and weaknesses of the various participating studies in terms of traits and covariates available for investigation, and suggest best uses for specific studies, such as examining the impact of a particular risk factor on a given genotype-phenotype association, or the risk of a specific trait associated with a given variant. An important product of PAGE II will be a collective dataset comprehensive of genotype and phenotype information, for use by the scientific community as a reference for population-based estimates of allele frequencies and association sizes across a broad range of phenotypes. The CC will lead the formatting, harmonizing, and disseminating of PAGE II data in one or more centralized datasets, including data cleaning and QC, and actively engage the Study Investigators in this process.
Approaches to genotyping quality control, phenotype harmonization, statistical analysis and data synthesis will be shared and reviewed in SC meetings. The SC will propose and agree upon approaches to establish an efficient cross-study analysis pipeline, with procedures and results to be standardized as much as feasible across participating studies and provided as rapidly as possible. These results will be compiled by the CC and provided to the scientific community through databases such as dbGaP or others to be developed through this program. Appropriate embargoes on submission of publications from these findings, consistent with NHGRI and NIH guidelines, will be applied. Investigative groups are required to share genotype and phenotype data on individual study participants in databases such as the controlled access portion of dbGaP, in keeping with NHGRI and NIH policies.
The SC will meet in person three times per year and monthly on conference calls as needed to share information on data resources, methodologies, analytical tools, as well as data and preliminary results. PAGE II will continue to have Working Groups in areas of interest to the awardees and the funding institute(s). Currently PAGE I has several such groups focused on phenotype harmonization and phenotype-specific analyses, along with committees focused on ethnicity/ancestry, data display and dissemination, statistical analysis, SNP selection and quality control, and implementation of the Metabochip pilot and subsequent scale-up. The tasks of the Working Groups will include, among other responsibilities: identifying common scientific areas and adjusting projects to accommodate shared interests, identifying novel projects that may result from synergy among the awarded groups, apprising the SC on progress, and identifying ways to interact with external ongoing networks and initiatives. Working Groups may propose new research collaborations with non-network investigators and organizations, as long as most or all PAGE sites have the opportunity to participate, according to criteria established by the PAGE SC. �Key co-investigators and pre- and postdoctoral trainees, in addition to the PD(s)/PI(s), will be eligible to attend SC meetings. PIs are encouraged to include investigators and trainees who are members of under-represented minority groups and those from different but related disciplines such as bioinformatics, public health, social sciences, and translational research where appropriate. The cost of 3-4 persons to attend these meetings, as well as the costs associated with monthly conference calls, should be included in the proposed research budget.
Data from this FOA are expected to be handled so as to increase the value of the significant public investment in genotyping and analysis in the participating population studies. NHGRI intends that descriptive study materials and data generated through genotyping efforts supported in this FOA will be widely shared with the scientific community for research uses through NIH-supported databases such as dbGaP. Although NHGRI expects these materials and data to be available through a database such as dbGaP, the NHGRI does not intend dbGaP, or any single database, to become the exclusive source of this program�s data; other databases, public web sites, and/or publication in the scientific literature may be suitable additional venues for data dissemination.
Applicants for this CC FOA should indicate their willingness to cooperate with Study Investigators supported under RFA-HG-12-010 and with NHGRI in the development and design of research and analysis methods, procedures, policies and strategies to be applied in this program. Applicants should also describe prior experience in working as part of a research consortium or other collaborative activities to meet individual study and collaborative goals.
Proof of appropriate informed consent and/or IRB approval for serving as the CC in this collaborative program, to use previously collected data and biospecimens for genetic research, and to share the resulting data, should be provided at the time of application submission. Only applications describing protection of participants� privacy and confidentiality will be considered.
Application Types Allowed
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.
NIH intends to fund 1 award, corresponding to a total of $800K, for fiscal year 2013. Future year amounts will depend on annual appropriations.
Individual application budgets should not exceed $800,000 total costs per year and must reflect actual needs of the proposed project.
Award Project Period
The total award period requested for this FOA may not exceed four 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.
Higher Education Institutions
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
Nonprofits Other Than Institutions of Higher Education
Non-domestic (non-U.S.) Entities (Foreign Institutions) are
not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.
Applicant organizations must complete the following registrations
as described in the SF 424 (R&R) Application Guide to be eligible to apply
for or receive an award. Applicants must have a valid Dun and Bradstreet
Universal Numbering System (DUNS) number in order to begin each of the following
All Program Director(s)/Principal Investigator(s) (PD(s)/PI(s))
must also work with their institutional officials to register with the eRA
Commons or ensure their existing eRA Commons account is affiliated with the eRA
Commons account of the applicant organization.
All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least 4-6 weeks prior to the application due date.
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 PD(s)/PI(s), visit the Multiple Program Director(s)/Principal Investigator(s) Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide.
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
Applicant organizations may submit more than one application, provided that each application is scientifically distinct.
NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed.
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, 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.
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:
The letter of intent should be sent to:
Lucia Hindorff, Ph.D., M.P.H.
National Human Genome Research Institute
National Institutes of Health
5635 Fishers Lane, Suite 3058, MSC 9307
Bethesda, MD 20892-9307
Rockville, MD 20852 (courier/FedEx/UPS)
The forms package associated with this FOA includes all applicable components, mandatory and optional. Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate �optional� components.
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
Resource Sharing Plan
Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide, with the following modification:
Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit in advance of the deadline to ensure they have time to make any application corrections that might be necessary for successful submission.
Organizations must submit applications via 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.
Applicants are responsible for viewing their application 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.
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. ��
Applications must be submitted electronically following the instructions described in the SF 424 (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.
All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF 424(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.
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 Central Contractor Registration (CCR). 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 by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete and/or nonresponsive will not be reviewed. �
In order to expedite review, applicants are requested to notify the NHGRI Referral Office by email at email@example.com when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.
Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.
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.
Reviewers will provide an overall impact/priority 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).
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?
How likely is the project to improve the assessment and expand the understanding of ancestral differences in disease associations with genomic variants of ancestral differences in SNP-disease associations?
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(s)/PI(s), do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?�
Are the plans for assisting with assessment of genotyping technologies, phenotype harmonization, providing logistical support and fulfilling other Coordinating Center functions likely to increase the synergy and productivity of the program? Are the plans to facilitate and organize the sharing of consortium data in a timely manner adequate?�
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?
If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?
Are the proposed approaches for phenotype harmonization and for collecting, collating, and disseminating information from investigative groups in one or more centralized datasets adequate? Are the proposed plans to share data in a timely manner likely to provide maximal scientific value for expanding understanding of ancestral differences in SNP-disease associations? ���
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?
Have the investigators documented their experience with working with large-scale population-based data, including familiarity with phenotype harmonization and statistical analysis in a highly-effective collaborative relationship? Does the PD(s)/PI(s) investigative team bring complementary and integrated expertise to the project, including biostatistics, epidemiology, and genetics/genomics, as applicable? Are the investigators willing to collaborate with each other, the NIH, and related existing efforts, including other NIH-funded and non-NIH funded programs in genome-wide studies, consistent with meeting the aims of this program? Is the bioinformatics infrastructure sufficient to accomplish the goals of the project? ����
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/priority score, but will not give separate scores for these items.
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 Human Subjects Protection and Inclusion Guidelines.
Inclusion of Women, Minorities, and Children
When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.
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.
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/priority score.
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) Genome Wide Association Studies (GWAS).
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.
Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the NHGRI, in accordance with NIH peer review policy and procedures, using the stated review criteria. Review assignments will be shown in the eRA Commons.
As part of the scientific peer review, all applications:
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 on Human Genome Research. The following will be considered in making funding decisions:
Additional criteria for award will include:
After the peer review of the application is completed, the PD(s)/PI(s) 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.
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 the DUNS, CCR Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.
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
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 will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.�
NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
The Project Scientist is a scientist of the NHGRI staff who will have substantial scientific and programmatic involvement during the conduct of this activity through technical assistance, advice, and coordination. However, the role of NIH staff 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 program and that NIH staff will be given the opportunity to offer input to this process. The Project Scientist will participate as a member of the SC and will have one vote. The Project Scientist will have the following substantial involvement:
Close interaction among the participating investigators will be required, as well as significant involvement from the NIH, to develop appropriate strategies and tools to design, perform, and analyze studies of ancestral differences in genomic variation associated with human diseases. The awardees and the Project Scientist will meet as the program SC three times per year and monthly on conference calls as needed to share information on data resources, methodologies, analytical tools, as well as data and preliminary results.� Key co-investigators and pre- and postdoctoral trainees, especially those who are members of under-represented minority groups or those from different but related disciplines, in addition to the PD(s)/PI(s), are eligible to attend these meetings.
The SC will serve as the main scientific body of the program.� The SC will be responsible for coordinating the activities being conducted by the program.� The SC membership will include one NHGRI Project Scientist and the PD/PI from each awarded cooperative agreement.� The SC may add additional members, and other government staff may attend the SC meetings as desired.� It is anticipated that additional coordination mechanisms may be set up with other U.S. and international groups that may collaborate with the program.
Each full member (PD/PI or NHGRI Project Scientist) will have one vote. �Awardee members of the SC will be required to accept and implement policies approved by the SC.
As described above, PAGE II will convene working groups to plan and implement cross-study activities.� The PAGE II SC will have the overall responsibility of assessing and prioritizing the progress of the various working groups. Awardees agree to work collaboratively to:
External Scientific Panel
An External Scientific Panel (ESP) will continue to evaluate the progress of the program. The ESP will provide recommendations to the National Advisory Council for Human Genome Research about the progress and scientific direction of all components of the program.
The ESP is currently composed of five senior scientists with relevant expertise, although in PAGE II the ESP may be augmented permanently or on an ad hoc basis as needed.� The ESP will continue to meet at least twice a year; some meetings may be conducted by telephone conference. Occasionally, the ESP may be asked to advise PAGE Investigators and the NHGRI on timely issues during the interim period between meetings.� At least once a year, there will be a joint meeting with the SC to allow the members of the both the ESP and the SC to interact directly.� Twice a year the ESP will make recommendations regarding progress of the program to the National Advisory Council for Human Genome Research about changes, if any, which may be necessary in the program.
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 to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the SC 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 the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.
When multiple years are involved, awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.
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.
Customer Support (Questions regarding Grants.gov registration and
submission, downloading or navigating forms)
Contact Center Phone: 800-518-4726
GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
eRA Commons Help Desk (Questions regarding eRA Commons registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
Lucia A. Hindorff, Ph.D., M.P.H.
National Human Genome Research Institute
Ken D. Nakamura, Ph.D.
National Human Genome Research Institute
National Human Genome Research Institute
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.
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.
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