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.

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 recent convergence of high-throughput genomic technologies, novel statistical methods and catalogues of genetic variants is finally allowing researchers to identify specific genes and gene networks that contribute to risk for psychiatric disorders. The repertoire of genetic signals (e.g. common variants, rare variants, copy number variants, gene expression and epigenetic) reproducibly associated with psychiatric disorders has expanded in the last few years through multiple large scale genome-wide analyses. It is increasingly clear that psychiatric disorders are influenced by many genes, most of which individually confer only small (e.g. common variants) to moderate (e.g. rare copy number variants and de novo single nucleotide variants) risk. Despite these fruitful discoveries, there is still a large gap in our understanding of how the combinations of these diverse risk factors lead to the development of highly complex and heterogeneous psychiatric disorders.

To gain an understanding of how these genetic interactions drive the complex neurobiological processes underlying pathophysiology of psychiatric phenotypes, there is a need to move beyond testing interactions of individual locus pairs to more comprehensive systems level approaches that integrate multiple domains of molecular information to decipher the molecular networks associated with cellular and circuit phenotypes. A few studies have already begun to synthesize such existing data; for example, genes associated with autism spectrum disorder (ASD) and schizophrenia (SCZ) have been shown to form co-expression networks during early human fetal cortical development, indicating their involvement in distinct biological functions during neurodevelopment and their relevance to psychiatric disorders. Given the rapid expanse of recently generated genomic data and the augmentation of basic knowledge of genomic function coming out of large scale genome-wide efforts, opportunities exist for leveraging these combined resources for novel discovery. The results of such analyses can then inform computer modeling and subsequent experimental validation of the complex pathways and networks that ultimately determine phenotypes from the cellular to whole organism level demonstrating their functional role in causality. Relevant phenotypes may go beyond a dichotomous clinical diagnosis to include dimensional constructs such as those described by the Research Domain Criteria (RDoC) project (http://www.nimh.nih.gov/research-priorities/rdoc/index.shtml).

This initiative will support studies that apply a combination of cutting-edge in silico approaches and biological experimentation strategies to evaluate in a reproducible and replicable manner the functional role of molecular networks in conferring susceptibility to severe mental illnesses. Though the primary focus of this initiative is analysis of existing data, applicants are expected to include, well-described follow-up strategies to test and confirm the findings. Since the goal is to test integrative computational and informatic approaches, it is understood that follow-up experiments may be limited in scope, however, demonstrating that the findings are replicable and have biological meaning is an essential component. Studies could focus on a comprehensive list of genetic signals and gene networks that have been consistently and reproducibly found to be associated with psychiatric phenotypes through genome-wide studies (e.g., DNA sequence variants, non-coding functional genomic elements, chromatin marks, eQTLs, epigenomic, trancriptomic, proteomic, metabolomic datasets). For integrative analysis and predictive network modelling to identify novel genetics factors or networks associated with psychiatric disorders, applicants are encouraged to use relevant existing data, including multi-scale psychiatric genomic data sets (preferably from well-phenotyped cohorts) and functional genomic data such as neural cell-type specific functional annotations, transcription factor binding sites, protein-protein interactions, chromatin conformation and structural data, post-translational functional regulatory annotations. To the extent possible investigators are encouraged to leverage existing datasets from efforts such as Brainspan, 1000 Genomes, CommonMind, PsychENCODE, ENCODE, Common Fund Epigenomics, IHEC, Psychiatric Genomic Consortium, and GTEx.

Examples of relevant research topics include, but are not limited to the following:

• Aggregate and mine large psychiatric multi-scale datasets with rich phenotypic information in combination with other genomic information (e.g. Brainspan, 1000 Genomes, CommonMind, PsychENCODE, ENCODE, Epigenomics, IHEC, Psychiatric Genomic Consortium, and GTEx, etc.) to identify novel genetic loci and gene networks and their functional role in psychiatric disorders.
• Determine how gene networks interact and converge across psychiatric phenotypes, including RDoC domains (e.g., through leveraging large clinical data systems with genomic information)
• Determine how molecular interactions are regulated across development, brain regions and cell-types to arrive at molecular networks driving critical neurobiological processes and neural circuits involved in the pathophysiology of psychiatric disorders.
• Evaluate critical gene networks at the protein level to elucidate the functional roles of the interaction network (e.g. through existing high-throughput methods)
• Pursue follow-up functional characterization of prioritized candidates identified through network predictive modeling approaches using experimental systems. This may include cell-based platforms such as induced pluripotent stem cells (iPSCs), in situ or in vivo systems.

The computational models predictions should be replicated using independent datasets and confirmed using biological measures from experimental data and approaches. Aside from the experimental work to provide evidence to assess the predictions, this FOA will NOT support large-scale data production or phenotyping, the establishment or maintenance of databases for prioritizing functional variants,, or approaches that simply aggregate information on variants. Since this initiative aims to identify biologically meaningful molecular networks underlying functional pathways relevant to psychiatric disorders, application that do not propose functional validation of computational models using biological outcomes existing and/or new experimental data will not be considered responsive to this FOA and will not be reviewed.

This FOA should be used when two or more collaborating sites are essential to complete the proposed research. For a linked set of collaborative R01 applications, each application must have its own Program Director/Principal Investigator (PD/PI) and the program must provide a mechanism for cross-site coordination and data sharing among the collaborating groups, quality control, database management, statistical analysis, and reporting. For each set of linked collaborative R01 applications, it is expected that each application will be coordinated and interlocked with the others as each application will contribute an essential component to the overall study.

 

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

• 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

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations
• Non-domestic (non-U.S.) Entities (Foreign Institutions)

Non-domestic (non-U.S.) Entities (Foreign Institutions) are 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

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.

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.

This FOA supports linked collaborative R01 applications. Multiple PDs/PIs are allowed on any single application. Because the collaborative R01 mechanism already supports a team approach between groups of experts across sites and collaborating applications, the designation of multiple PDs/PIs on a single application may be less likely to apply.  PD(s)/PI(s) from each linked application should NOT be designated as multiple PDs/PIs on each application of a collaborative set.

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.

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).

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.

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:

Geetha Senthil Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-402-0754
Fax: 301-402-4740
Email: [email protected]

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

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.

Descriptive Title of Applicant's Project: To allow NIH to identify a group of applications as a related set of collaborative R01s, the titles for each R01 in the set must have the following format:  a 1/N indicator + Identical title (e.g., 1/6-Multisite Comparison of Drug A vs. Drug B for Treatment of Disorder X , where the 1/6 means this is site 1 of 6 sites in the set.  The other sites will be labeled 2/6, 3/6, etc.).  Titles may not exceed 80 characters in length, including the tag, e.g., 1/6, at the beginning of the title.

Cover Letter Attachment: The Cover Letter is one pdf file only.  The following collaborative information is required in the Cover Letter:  a listing of all the applications that are a part of the set of collaborative R01s being submitted, including for each: 1) the PD/PI(s) name(s), 2) the Title (including the tag, e.g., 1/6 ), and 3) the Applicant Institution.  Each site should submit an identical listing

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

Facilities and Other Resources: Applicants are advised that the Facilities and Other Resources section should address not only physical resources, but also the intellectual and collaborative resources for executing the project. Instructions for this section include the following:

Describe how the scientific environment in which the research will be done contributes to the probability of success (e.g., institutional support, physical resources, and intellectual rapport). In describing the scientific environment in which the work will be done, discuss ways in which the proposed studies will benefit from unique features of the scientific environment.

For linked applications from multiple sites, each application must describe the resources available at that site. This should describe the individual applicant site and it is expected that this section of the application will be different in each of the linked applications as it is an opportunity to describe the unique features of the individual site.

Other Attachments: Linked applications must provide a single pdf attachment identical across linked applications that includes the following information:

1) Project Management Plan Section must include a detailed description of how different elements of the project would operate in a synergistic and integrated manner, leadership structure, overall managerial and administrative responsibilities, and cross-site comparability of training to assure reliability and quality control, data coordination across sites, authorship rights for publications; process for arbitrating disagreements on publication and other issues; completion of the research project should a key member leave the Group.

All instructions in the SF424 (R&R) Application Guide must be followed.

It is expected that the projects will include synergistic and collaborative research teams comprised of outstanding scientists from diverse scientific disciplines with expertise in computational statistical methodologies, neurodevelopment, functional neurobiology, protein biochemistry, genetics and/or other relevant areas, as well as expertise and understanding of the complexities of psychiatric genomics. In recognition of the multidisciplinary nature of the approach, Multiple PD/PI applications are encouraged from investigators with prior experience in coordinating collaborative research. Inclusion of multidisciplinary research team with investigators having prior experience with large genomic efforts (e.g. Brainspan, 1000 Genomes, CommonMind, PsychENCODE, ENCODE, Common Fund Epigenomics, IHEC, Psychiatric Genomic Consortium, and GTEx) is encouraged.

All instructions in the SF424 (R&R) Application Guide must be followed. Justify the allocation of funds and resources among development of computational methods, generation of computational predictions and functional analysis.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Specific Aims: Include an Overview section as part of the specific aims attachment. This attachment must provide: 1) an overall rationale for applying as a collaborative study; 2) outline the role of each site and how they will contribute to achieve the FOA objectives; 3) Specific Aims of the collaborative project including a concise description of aims with a clear justification for the in silico and experimental approaches being used.

This Specific Aims attachment must be identical in each of the applications that are linked together in a collaborative R01 set.

Research Strategy: Applications from each site must contain a Research Strategy that clearly describes those aspects of the project that are common to all sites of the collaboration.

The Research Strategy must be identical across linked collaborative R01 applications with the exception of the section under the header "Elements Unique to This Site." All variations in the Research Strategy between sites, no matter how minor, should be highlighted in a subsection of the Research Strategy with the heading "Elements Unique to This Site" (estimated to be no more than 1 page of the Research Strategy Section). In this subsection PDs/PIs should describe, for example, how the research site has a unique role in the collaboration, such as data coordination, statistical analyses, etc. Any site that contracts out some portions of this work should list this fact under "Elements Unique to This Site," and provide a full description of the nature, purpose and oversight of this contractual arrangement.

Applications must conform with current guidelines taking care to address important elements related to Significance, Approach, and Innovation. As a part of the Research Strategy section, applicants are requested to clearly address the following aspects:

• Describe the status of current research efforts, how the proposed methods are expected to compare to other methods that address the same question, and/or how the research questions posed relate to the objectives of the FOA.
• Applicants are encouraged to apply cutting-edge computational approaches to identify and confirm novel genetic factors leveraging existing high quality human genomic data from well-phenotyped cohorts with highly heritable psychiatric disorders.
• Highlight any novel features of the project that address technical or conceptual limitations of the current state of the art.
• Provide sufficient details on in silico-methods and describe any development of software for the in silico analysis and features designed to facilitate broad use.
• Describe the datasets to be used for in silico analysis and how they will be obtained.
• Describe how the biological measures from existing and/or new experimental data will inform computational predictions and allow for reassessing the computational models
• Provide sufficient details on the replication and functional follow-up studies and provide justification on appropriateness of such assessments to validate the computational/modeling approaches proposed.
• For any functional analysis, describe how the experimental systems assay(s) are suitable, well-validated and cost-effective for the intended purpose.
• Where relevant, describe the scalability of the computational and/or functional methods and justify the trade-offs between higher throughput and physiological relevance.
• Provide evidence of feasibility of the proposed studies, based on preliminary data as well as qualifications and track record of the key personnel for performing critical aspects of the research study (e.g., computational methods, functional analysis).
• Explain how the functional assays test the specificity and sensitivity of the computational predictions. Provide a level of detail commensurate with the amount of resources being allocated to the functional analysis.
• Provide appropriate and sufficient details commensurate with the relative emphasis of computational versus functional approaches
• Describe strategies for functional validation of computational models using biological outcomes from existing and/or new experimental data. Describe rationale for the computational models and biological endpoints chosen for functional validation.
• A "Timeline and Milestones Section" should be included in the Research Strategy attachment of the application. Milestones should be well-described, specific, measurable, and scientifically justified milestones and benchmarks. This section should describe the timeline for all major steps in the project, with particular emphasis on when/how computational analysis transitions to experimental analysis. The milestones should be considered to evaluate progress and direction of the project and should not be just a restatement of the specific aims.
• Investigators are encouraged to leverage existing large-scale, genome-wide data sets from efforts such as Brainspan, 1000 Genomes, CommonMind, PsychENCODE, ENCODE, Common Fund Epigenomics, IHEC, Psychiatric Genomic Consortium, and GTEx

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, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

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.

When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

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.

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 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.

Important reminders:
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 NIMH Referral Office by email at [email protected] when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.

Applications must be submitted as a linked group or set of R01s, usually one R01 per participating PD(s)/PI(s). For each set of linked collaborative R01 applications, it is expected that each application will be coordinated and interlocked with the others as each application will contribute an essential component to the overall study.

NIMH encourages the use of common data elements (CDEs) in basic, clinical, and applied research, patient registries, and other human subject research to facilitate broader and more effective use of data and advance research across studies. CDEs are data elements that have been identified and defined for use in multiple data sets across different studies. Use of CDEs can facilitate data sharing and standardization to improve data quality and enable data integration from multiple studies and sources, including electronic health records. NIH ICs have identified CDEs for many clinical domains (e.g., neurological disease), types of studies (e.g. genome-wide association studies (GWAS)), types of outcomes (e.g., patient-reported outcomes), and patient registries (e.g., the Global Rare Diseases Patient Registry and Data Repository). NIH has established a Common Data Element (CDE) Resource Portal" (http://cde.nih.gov/) to assist investigators in identifying NIH-supported CDEs when developing protocols, case report forms, and other instruments for data collection. The Portal provides guidance about and access to NIH-supported CDE initiatives and other tools and resources for the appropriate use of CDEs and data standards in NIH-funded research. Investigators are encouraged to consult the Portal and describe in their applications any use they will make of NIH-supported CDEs in their projects.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.

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 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? Do the methods proposed have the potential to provide new transformative insights into understanding the molecular networks and complex pathways that confer susceptibility to severe mental illnesses?  Are the plans sufficiently bold to constitute a substantial advance in the ability to characterize functional relevance of gene networks?

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 they have prior experience with consortia and datasets from large genomic efforts such as Brainspan, 1000 Genomes, CommonMind, PsychENCODE, ENCODE, Common Fund Epigenomics, IHEC, Psychiatric Genomic Consortium, and GTEx? Do the PD(s)/PI(s) and other key personnel have adequate expertise in computational statistical methodologies, neurodevelopment, functional neurobiology, protein biochemistry, genetics and/or other relevant areas, as well as expertise and understanding of the complexities of psychiatric genomics? Do the PD(s)/PI(s) have prior experience with coordinating collaborative research? Is there complementary and synergistic expertise across the sites? Will the leadership plan optimize the management of a milestone-driven, multidisciplinary project?

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? Is the application proposing innovative ways to lay the foundation for computational modeling and experimental confirmation of the complex pathways and networks that ultimately influence the risk for mental illness? If successful, will the proposed project identify molecular mechanisms driving neurobiological processes underlying psychiatric phenotypes?

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?  Are the methods being applied to existing human genomic and phenotypic data from well-phenotyped cohorts with highly heritable psychiatric disorders? Does the project include cutting-edge computational approaches to identify and evaluate novel genetic factors and molecular networks underlying susceptibility to psychiatric disorders? Does the project use high quality datasets for the proposed analyses? Are the functional follow-up studies described in sufficient detail? Does the project include strategies to replicate findings from computational model predictions? Are the functional/biological studies appropriate to confirm the computational/modeling approaches proposed? Are the in silico-methods described in sufficient detail?

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?

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 research plan justify the need for a collaborative multi-site project using this FOA? Are sufficient and feasible mechanisms in place to ensure collaboration across sites to achieve scientific integration of research procedures, overall managerial and administrative responsibilities, appropriate quality control and reliability assurance, and planning for data management, analysis and reporting of results? Does the application description address data coordination across linked applications? Does the application provide a description of the leadership structure across the linked applications? Are there adequate plans for shared decision making among PDs/PIs with regard to personnel, changes in research activities? Does the description address frequency and type of contact between participating researchers; specification of leadership roles across linked applications; and a description of whether particular individuals or sites will coordinate specialized subcomponents of the research plan? Does the application describe processes for joint decision-making regarding research activities and publication, as well as procedures for resolving disagreements and grievance?

Does the application include well described, specific, measurable, and scientifically justified milestones and benchmarks? Does the application provide timeline for all major steps in the project, with particular emphasis on when/how computational analysis transitions to experimental analysis to achieve the goals of the FOA?

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.

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.

Not Applicable

Not Applicable

Not Applicable

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.

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

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).

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.

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 NIMH 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 Mental Health Council. 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.

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.

Projects awarded under this FOA and the companion FOA will form PsychGenNET consortium to accelerate scientific progress through the coordination of research strategies, analytical methods and data with other research groups within the consortium to address the aforementioned research objectives of the FOA.

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.

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

Not Applicable

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) 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.

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: http://grants.nih.gov/support/index.html
Email: [email protected]

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact CenterTelephone: 800-518-4726
Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-710-0267

Geetha Senthil, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-402-0754
Email: [email protected]

David M. Panchision, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-443-5288
Email: [email protected]

Andrea Beckel-Mitchener, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-443-5288
Email: [email protected]

David Armstrong, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-443-3534
Email: [email protected])

Terri Jarosik 
National Institute of Mental Health (NIMH)
Telephone: 301-443-3858
Email: [email protected]

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 Part 75.