Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	National Institute of Mental Health (NIMH)
Funding Opportunity Title	Unveiling the Genome: Genetic Architecture of Severe Mental Disorders Revealed (Collaborative U01)
Activity Code	U01 Research Project -- Cooperative Agreements
Announcement Type	New
Related Notices	February 20, 2015 - Notice of Expiration of PAR-13-241.See Notice NOT-MH-15-011. June 4, 2014 - Notice NOT-14-074 supersedes instructions in Section III.3 regarding applications that are essentially the same. August 21, 2013: Removed reference to ASSIST in section IV.3, since ASSIST is currently only available for multi-project applications. May 30, 2013 (NOT-OD-13-074) - NIH to Require Use of Updated Electronic Application Forms for Due Dates on or after September 25, 2013. Forms-C applications are required for due dates on or after September 25, 2013.
Funding Opportunity Announcement (FOA) Number	PAR-13-241
Companion Funding Opportunity	None
Number of Applications	See Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.242
Funding Opportunity Purpose	The purpose of this Funding Opportunity Announcement (FOA) is to support a consortium of collaborative projects, with a minimum of two sites, that propose to use cutting edge technologies to generate and analyze whole genome sequencing (WGS) data from either case control or family samples in order to elucidate the full genetic architecture underlying susceptibility to severe mental disorders. Insights into the genetic architecture underlying susceptibility to severe mental disorders will be achieved through implementation of state of the art WGS assays and innovative/novel statistical methods.

Posted Date	June 7, 2013
Open Date (Earliest Submission Date)	January 13, 2014
Letter of Intent Due Date(s)	30 days before the application due date
Application Due Date(s)	February 13, 2014; October 15, 2014; October 15, 2015, by 5:00 PM local time of applicant organization. Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.
AIDS Application Due Date(s)	Not Applicable
Scientific Merit Review	June 2014, February 2015, February 2016
Advisory Council Review	August 2014, May 2015, May 2016
Earliest Start Date	September 2014, July 2015, July 2016
Expiration Date	New Date February 20, 2015 per issuance of NOT-MH-15-011. (Original Expiration Date: October 16, 2015 )
Due Dates for E.O. 12372	Not Applicable

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 purpose of this Funding Opportunity Announcement (FOA) is to provide support for collaborative cooperative agreement applications that propose to use cutting edge technologies to generate and analyze whole genome sequencing (WGS) data from either case control or family samples in order to elucidate the full genetic architecture underlying susceptibility to severe mental disorders.

Severe mental disorders have high heritability and represent a huge public health burden. For example, schizophrenia, which is characterized by hallucinations, delusions and impaired cognition, has a lifetime risk of 1% in the general population and heritability is estimated to be approximately 80%. Mental disorders, as with most complex human traits, are influenced by numerous genes that each have small individual effects, as well as environmental influences. Since 2007, numerous robust and replicable genetic findings have been reported for psychiatric disorders. These advances have mostly been through genome-wide association studies (GWASs) and structural variation studies. Though these results meet the standards in human genetics for significance and replication, taken together, these associations fail to explain a substantial proportion of the heritability of the complex phenotypes studied; this phenomenon has been referred to as the "missing heritability problem." A comprehensive portrait of genetic architecture does not now exist for any psychiatric disorder. Gaining a more complete knowledge of the specific loci involved in disease etiology is of great importance. Rapidly evolving genomic technologies combined with the availability of increasingly large study cohorts have led to a series of highly reproducible findings, highlighting the contribution of rare variation in both DNA sequence and chromosomal structure, and placing limits on the risk conferred by individual, common genetic polymorphisms. Much work remains to be done in elucidating the full genetic architecture of these highly heterogeneous brain diseases. With the rapid advances in genomic technologies that are now available, whole genome sequencing (WGS) has become a feasible strategy for investigation into these complex disorders. WGS can detect structural variation of all types, ranging from gross chromosomal rearrangements to copy number variants (CNV) and insertion deletions (indels), while also providing highly sensitive single-base resolution. Further, in light of the recent discoveries from the ENCODE project (http://www.genome.gov/10005107), linking up to 80% of the genome to a specific biological function, it is timely to direct more efforts into exploring all types of variation across the genome, particularly non-coding regulatory variants.

This initiative aims to support studies that apply cutting edge WGS technologies to previously collected samples of well-characterized highly heritable severe mental disorders (e.g. schizophrenia, bipolar disorder, etc.) in order to identify a full range of genetic variation, from single-nucleotide variants to large structural variants, in coding and non-coding regions, etc. The goal of this FOA is to leverage existing cohorts and samples, such as those available in the NIMH repository https://www.nimhgenetics.org/, rather than to support new sample collection. Under the award, the investigator will produce whole genome sequencing data and lead comprehensive analyses to identify the genomic contributions to both risk for and/or protection against severe mental disorders. Given the expanse of data generated through WGS, use of innovative and/or novel analytical strategies incorporating sophisticated statistical approaches is strongly encouraged.

Applications submitted to this FOA should describe the capabilities for sequence production, quality control (QC), storage, data analysis, and annotation accuracy to distinguish between sequencing errors and real polymorphisms along with a time line for accomplishing the stated goals, and the costs related to the sequencing and analysis. In the description of the data analyses, the investigator should consider phenotypes, disease-related covariates, and significance of association with the disease for common, rare, and unique sequences. The investigator should also describe how structural rearrangements, insertions, deletions, and haplotypes as genomic changes will be analyzed and correlated with disease status.

This FOA encourages collaborative grant applications, including a minimum of two sites (i.e. two linked applications), for research in a number of critical areas including, but not limited to:

• Family-based designs with a minimum of two parents and an affected offspring to allow determination of both inherited and de novo variation that may contribute to disease susceptibility. Studies including larger, multiplex pedigrees are also encouraged.
• Case-control studies that investigate a broad range of genomic elements identified through WGS that may, in combination, play a role in the etiology of severe mental illness using cutting edge or novel genomic, bioinformatic and analytic approaches and platforms.

Applications must address the leadership structure across linked applications and how data coordination will be handled. Essential elements include frequency and type of contact between participating researchers and specification of leadership roles and whether or not particular individuals or sites will coordinate specialized subcomponents of the research plan (e.g., genetic processing and analysis). The data coordination plan should also include information about processes for joint decision-making regarding research activities and publication, as well as procedures for resolving disagreements and grievance.

Funding Instrument	Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities.
Application Types Allowed	New Resubmission Revision Renewals The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications. The NIMH intends to commit approximately $4,000,000 in FY 2014 to fund 1-2 collaborations with a minimum of 2 sites each.
Award Budget	Application budgets are not limited, but need to reflect the actual needs of the proposed project.
Award Project Period	The total project period may not exceed 4 years.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

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 (PDs/PIs)

All PDs/PIs must have an eRA Commons account and should work with their organizational officials to either create a new account or to affiliate an existing account with the applicant organization’s eRA Commons account. 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 requires the use of the linked NIH Collaborative Cooperative Agreement (U01) award mechanism .Multiple PDs/PIs are allowed on any single application. Because the collaborative U01 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.

NIH will not accept any application that is essentially the same as one already reviewed within the past thirty-seven months (as described in the NIH Grants Policy Statement), except for submission:

• To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;
• Of an investigator-initiated application that was originally submitted to an RFA but not paid; or
• Of an application with a changed grant activity code.

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:

• 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:

Thomas Lehner Ph.D., M.P.H.
Office of Genomics Research Coordination
National Institute of Mental Health (NIMH)
6001 Executive Boulevard, Room 7189, MSC 9643
Bethesda, MD 20892-9643
Rockville, MD 20852 (for courier/express mail service)
Telephone: 301-443-9869
FAX: 301-402-4740
Email: tlehner@mail.nih.gov

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

The forms package associated with this FOA includes all applicable components, required 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 instructions in the SF424 (R&R) Application Guide must be followed with the following additional instructions:

Descriptive Title of Applicant's Project: To allow NIH to identify a group of applications as a related set of collaborative U01s, the titles for each U01 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.

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:

Facilities and Other Resources: Applicants are advised that the Facilities and Other Resources section, which should address not only physical resources, but also the intellectual and collaborative resources for executing the project [see Section 4.4, Facilities & Other Resources of the SF424 (R&R)] can be utilized to address relevant Resource-related collaborative issues. 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 of subject populations or will employ useful collaborative arrangements.
• If there are multiple performance sites within a single application, describe the resources available at each site.

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:

The PHS Cover Letter is one pdf file only. Therefore, it must include the information requested below on the collaborative sites, as well as the Institute approval on linked applications that, when combined, are at or exceed $500,000 direct costs in any year of the budget. 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 U01s being submitted, including for each: 1) the PD(s)/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, with the following additional instructions:

Introduction to Application: For Resubmission and Revision applications, an Introduction to Application is required in the Overall component. This should detail how the application has changed from the previous version. Resubmissions must include responses to criticisms and issues raised in the Summary Statement of the first submission.

Specific Aims: The application from each site must contain an identical OVERVIEW that is included with the Specific Aims attachment. The overview should provide an overall rationale for applying as a collaborative study; the role of each site; the approach to project management; and any important unique elements to any of the sites. Provide a concise description of overall project aims. Outline how each of the sites will contribute to attaining objectives. The renewal should state how, or if, specific aims have changed from the previous funding period.

Research Strategy:

• Applications must describe a feasible mechanism for scientific integration of research procedures, overall managerial and administrative responsibilities, and cross-site comparability of training to assure reliability and quality control.
• The Research Strategy must include a description of those aspects of the project that are common to all sites of the collaboration.
• Investigators should use this section to describe the research procedures or protocol, the study population from which samples are drawn, data analyses, and any other characteristics that support each site’s importance to the overall project.
• All variations in the research strategy between sites, no matter how minor, should be highlighted in a subsection with the heading "ELEMENTS UNIQUE TO THIS SITE." 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 EACH SITE," and provide a full description of the nature, purpose and oversight of this contractual arrangement.
• Plans for ensuring: access to data by all sites; analytic resources; publication and authorship rights; rapid availability for public use of research materials and other means of distributing research materials to the wider scientific community; and a process for arbitrating disagreements on publication and other issues, should be included in the application.

As part of the APPROACH:

The application should describe the capabilities for sequence production, quality control (QC), storage, data analysis, and annotation accuracy to distinguish between sequencing errors and real polymorphisms along with a time line for accomplishing the stated goals, and the costs related to the sequencing and analysis.

• In the description of the data analyses, the investigator should consider phenotypes, disease-related covariates, and significance of association with the disease for common, rare, and unique sequences. The investigator should also describe how structural rearrangements, insertions, deletions, and haplotypes as genomic changes will be analyzed and correlated with disease status.
• Applications must address the leadership structure across linked applications and how data coordination will be handled. A Steering Committee comprised of all PDs/PIs and key personnel, science and project officers from NIMH, will be formed. Essential elements include frequency and type of contact between participating researchers and specification of leadership roles and whether or not particular individuals or sites will coordinate specialized subcomponents of the research plan (e.g., genetic processing and analysis). The data coordination plan should also include information about processes for joint decision-making regarding research activities and publication, as well as procedures for resolving disagreements and grievance

As part of INNOVATION:

• Applications must explicitly demonstrate how the proposed collaborative work will address questions that would be difficult to answer with data from a single site or study.
• Feasibility of achieving the collaborative goals must be supported with sufficient information about sample size and demographics, including an inventory of existing genetic samples and phenotypic measures and justification for collection of new data.

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 modifications:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data and Resource Sharing Plan.
• Applicants should provide a specific proposal for release of production data in the application, and are encouraged to address the issue of the release of data analyses. The reasonableness of the proposed data sharing plan will be assessed by the reviewers who will provide their assessment of the proposed data sharing plan as an administrative note and will not factor it into the determination of scientific merit or the impact score. After the initial review, NIMH program staff will be responsible for any additional administrative review of the plan for sharing data and may negotiate modifications of the data sharing plan with the prospective awardee before recommending funding of an application. The adequacy of the negotiated data sharing plan will be considered by program staff when making funding recommendations

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.

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.

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 by the Center for Scientific Review, NIH. Applications that are incomplete will not be reviewed.

In order to expedite review, applicants are requested to notify the NIMH Referral Office by email at NIMHReferral@mail.nih.gov when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.

Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A), OR $500,000 or more in direct costs for the COMBINED budgets across the linked applications, must contact NIH program staff at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF424 (R&R) Application Guide.

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 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.

Significance

Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? Does the proposed work have the potential to identify novel genetic risk variants associated with mental illness through comprehensive analyses? Are the plans sufficiently bold to constitute a substantial advance in the ability to analyze whole genome sequencing data? Does the proposed work have a strong likelihood of revealing the structure of the genome of subjects with severe mental illness?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project? Do the data and expertise of the participating PDs/PIs complement each other and provide synergism to the study? Are the track records of the PD(s)/PI(s) and other key personnel in the production and analysis of high-throughput sequencing data adequate to conduct the proposed research successfully?

Innovation

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 there innovative strategies for analysis of whole genome sequencing data that will lead to the development of new paradigms for analyzing genotype-phenotype relationships in psychiatric genetic research?

Approach

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?

For the samples proposed to be studied, are the DNA samples of sufficiently high quality to anticipate high quality sequencing results? Does the proposed technology address sequence quality and the sequencing of entire genomes? Is the approach to the analysis of sequencing data well developed and well-informed, relative to the state of the technology? Are there clear plans for validation of novel rare and de novo variants that are discovered? Are the timeline and milestones logical and realistic? Are key technical barriers and dependencies identified?

Environment

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.

Collaboration

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? Are there adequate plans for shared decision making among PDs/PIs with regard to personnel, clinical decisions, changes in study protocol, and authorship?

Leadership Structure and Data Coordination

Does the application provide a full description of the leadership structure across the linked applications as well as a data coordination plan? 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 (e.g., genetic processing and analysis, development of neurocognitive indices)? Does the data coordination plan include information about processes for joint decision-making regarding research activities and publication, as well as procedures for resolving disagreements and grievance?

Feasibility

Is sufficient information provided about sample size and demographics, including an inventory of existing genetic samples and phenotypic measures? If new data collection is proposed, is the justification appropriate and compelling?

Scientific Synergies

Does the application explicitly demonstrate how the proposed collaborative work will address questions that would be difficult to answer with data from a single site or study?

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.

Vertebrate Animals

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.

Biohazards

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.

Resubmissions

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Renewals

For Renewals, the committee will consider the progress made in the last funding period.

Revisions

For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

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.

Applications from Foreign Organizations

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.

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 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.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications. 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.

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, SAM 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:

• The PD/PI(s) will have primary authority and responsibility to define objectives and approaches and to plan and conduct the proposed research. She/he will assume responsibility and accountability to the applicant organization and to the NIMH for performance and proper conduct of all research supported in this initiative, including the NIH intramural component, if applicable, in accordance with the Terms and Conditions of Award. The grantees will coordinate and attend at least monthly Steering Committee (SC) meetings. The SC will set research priorities and milestones, decide optimal research approaches and protocol designs, and contribute to the adjustment of research protocols or approaches as warranted. The PIs agree to accept the close coordination, cooperation, and participation of a NIMH Project Scientist in the SC to facilitate coordination amongst the grantees and other projects with related goals.
• NIH intramural research scientists participating as senior/key personnel have the same rights and responsibilities as other senior/key personnel (see below for Participation of NIH Intramural Scientists).
• The Awardee Institution and/or PD/PI's Institution will retain primary custody of and have primary rights to data as specified under the NIMH approved data and research resource sharing plans (described above). These plans should include sharing clinical and genotypic data with the NIMH Center for Collaborative Genomic Studies, genotype-phenotype data with the database of Genotypes and Phenotypes (dbGaP), and/or clinical and associated genotype and phenotype data associated with autism spectrum disorders to the National Database for Autism Research (NDAR), as appropriate. The Government, via the NIMH Project Scientist(s), will have access to data generated under this cooperative agreement and may periodically review the data consistent with current DHHS, PHS, and NIH policies. Timely publication of major findings by the Group members is strongly encouraged. Publication or oral presentation of work done under this agreement will be accompanied by appropriate acknowledgment of NIMH support, including the assigned cooperative agreement award number.
• Ownership of all analytic tools, protocols and assays developed during the course of the research rests with the respective PI(s) who generated them. Awardees will follow the NIMH approved research resource and data sharing plans.

NIH staff members have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

A. The NIMH Project Scientist (or designated alternate in the event the Project Scientist is not available) will have substantial programmatic/scientific involvement that is above and beyond the normal stewardship role in awards, as described below:

• Participate as an active voting member of the SC during meetings and in conference calls.
• Serve as a resource with respect to other ongoing NIH activities that may be relevant to this effort and providing expert advice to the awardees on specific scientific and/or analytic issues.
• Assist in the design, development, and coordination of the different stages of the study within their role as a participant on the SC.
• Review analysis plans to ensure that they are within the scope of this effort and consistent with the results of peer review.
• Coordinate and review with the assistance of the PD(s)/PI(s) the timeline for processing procedures, data submission and integration, and distribution to approved investigators.

B. The NIH Project Scientist (or designated alternate in the event the Project Scientist is not available) will assist and facilitate the SC group process but not direct it. The Project Scientist will retain the option to recommend additional research endeavors within the constraints of the approved research and negotiated budget. To help carry out these duties, the Project Scientist may consult with non-NIH experts in the field.

C. The NIMH Program Officer has usual stewardship responsibility for monitoring the conduct and progress of the project. The Program Officer carries primary responsibility for periodic review and approval of the study protocol in relation to stated recommendations regarding continuance of the project, receives all required reports and determines that satisfactory progress is being made, and attends the SC meetings as a non-voting participant.

Participation of NIH Intramural Scientists. An NIH intramural scientist may serve as a co-investigator, collaborator, or consultant. However, an Intramural scientist may not receive salary, equipment, supplies, or other remuneration from awards resulting from this FOA. The Intramural scientist must obtain written approval of his/her NIH Institute Scientific Director for the amount of resources that may be allocated to the project. The approval must also specify that the conduct of the project will comply with the DHHS regulations for research involving human subjects (if applicable) and with the PHS policy on vertebrate animal research. The participation of an intramural scientist is independent of and unrelated to the role of the NIMH Project Scientist. The involvement of Intramural scientists needs to be consistent with NIH Policy and all applicable federal laws and regulations: http://www1.od.nih.gov/oir/sourcebook/ethic-conduct/ethical-conduct-toc.htm.

Areas of Joint Responsibility include:

The SC is composed of the PDs/PIs, the NIMH Project Scientist (or alternate), and the NIMH Program Officer. Additional members may be added at the discretion of the SC. The SC will set research priorities and milestones, decide optimal research approaches and protocol designs, periodically review progress, and contribute to the adjustment of research protocols or approaches as warranted. The PDs/PIs will select a chair of the SC amongst themselves. It is expected that decisions made or actions taken by the SC will be by consensus, or majority vote when needed; the members of the SC will each have one vote, with NIMH Project Scientist (or alternate) having one vote. The NIMH Program Officer will not have a vote. Meetings of the SC will be held monthly by teleconference calls, with an expected yearly meeting in person. Outside consultants/experts may be asked to participate in SC meetings and discussions, but not have a vote on committee decisions. Membership on the SC becomes effective upon issuance of the Notice of Grant Award.

Dispute Resolution:

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 Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in 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 annual Non-Competing Progress Report (PHS 2590 or RPPR) 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)

Web ticketing system: https://public.era.nih.gov/commonshelp
TTY: 301-451-5939
Email: commons@od.nih.gov

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726

Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone: 301-710-0267
TTY 301-451-5936
Email: GrantsInfo@nih.gov

Thomas Lehner Ph.D., M.P.H.
National Institute of Mental Health (NIMH)
Telephone: 301-443-9869
Email: tlehner@mail.nih.gov

David Armstrong, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-443-3534
Email: armstrada@mail.nih.gov

Terri Jarosik
National Institute of Mental Health (NIMH)
Telephone: 301-443-3858
Email: tjarosik@mail.nih.gov

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.