Notice Number: NOT-CA-08-011
Key Dates
Release Date: March 5, 2008
Issued by
National Cancer Institute (NCI) (http://www.cancer.gov) on behalf of the National Institutes of Health (NIH) (http://www.nih.gov).
Purpose
On behalf of the NIH, the NCI is announcing the availability of administrative supplements for NIH-funded genetic association studies, aimed at identifying genetic factors involved in complex trait etiology. The purpose of this funding opportunity is to provide support for replication studies (with or without fine-mapping) of genetic regions putatively associated with the studied complex trait(s). This opportunity for eligible NIH award holders to request administrative supplement support was developed as part of the NIH-wide Genes, Environment, and Health Initiative (GEI, http://www.gei.nih.gov/). All NIH Institutes and Centers participate in NIH-wide initiatives.
This opportunity to request administrative supplement support will be open to all current NIH awardees of R01, P01, and P50 grants and U01, U19, and U54 cooperative agreements provided that the following conditions are met:
1) The “parent” award must be for a project or program involving genetic association studies (preferably involving a genome-wide association, or “GWA,” component), well described and justified in terms of evidence for genetic factors contributing to disease susceptibility and/or trait variation, appropriateness of the proposed study design and study population, definition of case and control status (assuming population-based design), power of the sample set to detect a genetic effect, and analysis plan;
2) Any phenotype can be proposed for investigation in the supplement request, provided it is related to the phenotype proposed and reviewed in the original award (NOTE: Acceptable phenotypes need not be cancer or cancer-related);
3) The proposed replication study or fine-mapping effort must be clearly within the scope of the peer-reviewed “parent” award without duplication of efforts (NOTE: The proposed replication study or fine-mapping effort may not be currently supported by NIH or any other funding agency);
4) The “parent” award must remain active during the entire funding period of this supplement; and
5) The Principal Investigator (PI) for the supplement must be the PI of the “parent” award.
To date, numerous genome-wide association studies (GWAS) of complex traits have yielded promising results. However, follow-up studies are needed to eliminate false positives, extend the findings to diverse populations (diverse in terms of ethnicity or environmental exposures) and related phenotypes, and narrow the association interval. The purpose of this funding opportunity is to provide support for replication and fine-mapping studies of genetic regions putatively associated with the studied complex trait(s) (primarily those identified by GWA studies), with the aim of maximizing the productivity of NIH-funded GWAS. The overall goal of these efforts is to advance our understanding of the roles of genetic and environmental factors in complex disease etiology.
For this opportunity, “replication” is defined as assaying a subset of the most strongly associated single nucleotide polymorphisms (SNPs) or other genetic variants in one or more additional study populations. Fine-mapping is defined as additional genotyping of SNPs or other genetic variants not included in the original genotyping platform for a gene or region that has been replicated as associated with a disease or trait.
A replication study alone or a replication study plus a fine-mapping effort may be proposed. Fine-mapping alone would be considered non-responsive.
This funding opportunity includes support for:
- Genotyping of select genetic polymorphisms;
- Specimen preparation and transfer;
- Data analysis; and
- Modest amount of additional support for the PI or new collaborators, if needed to bring in the replication study populations.
Priority in funding will be given to studies with one or more of the following characteristics:
- Synergy with NIH’s Gene Environment Association studies (GENEVA, RFA HG-07-014, http://www.genevastudy.org, see NIH press release at http://genome.gov/26022424);
- Breadth of available phenotypic (disease susceptibility or trait variation) and exposure measures for study participants and plans for sharing data with the research community through databases such as dbGAP (http://www.ncbi.nlm.nih.gov/sites/entrez?db=gap);
- Focus on replication in original discovery population, if little replication information is available to date (e.g., a study that focused on replicating “hits” in a recent GWAS using a similar study population); and
- Focus on populations not included in the initial GWAS or subsequent replication studies, such as a group with different exposures, as these environmental differences may be an important reason why some GWAS results do not replicate across studies;
- Focus on populations not included in the initial GWAS or subsequent replication studies, such as a different race/ethnic group (e.g., priority would be given to a study that focused on populations of African origin for associations that have been discovered and replicated in populations of European ancestry);
NOTE: These supplements are not intended to support discovery genome-wide association efforts; however, consideration may be given to trying to find resources within or outside GEI to perform such a study in very well-characterized participants in populations other than those studied to date. This possibility would depend on finding sufficient funds so as not to impede other GEI replication efforts, or on reprogramming GEI funds with the approval of the NIH GEI Coordinating Committee.
Investigators will be encouraged to accept genotyping support through an NIH GEI-funded genotyping center, but could have the option of accepting support through the investigator’s award, assuming they could provide adequate justification including data quality and cost-effectiveness.
If an award is made, the applicant institution would be expected to make de-identified individual-level genotype and phenotype data publicly available for approved research purposes within the NIH GWAS data repository, dbGAP, at the NIH National Center for Biotechnology Information (NCBI) (as described in NIH Guide Notice NOT-OD-07-088, Policy for Sharing of Data Obtained in NIH Supported or Conducted GWAS).
Detailed submission instructions are provided in the Submission Guidelines (http://cancercontrol.cancer.gov/funding_apply.html#egrp). Briefly, the request should be submitted using the format of PHS 398 application kit. It should contain sufficient detail (similar to a standard research application but not to exceed 5 pages) to allow the NIH staff members to assess the scientific merit of the proposed replication or fine-mapping study and the appropriateness of the request for supplemental funding. Specifically, applicants should provide detailed summary information regarding the GWAS that identified the genetic regions as being associated with the disease or trait and why the regions should be a priority for a replication study. Applicants should summarize known/documented replication efforts, whether published, in progress, or planned. The replication study population should be well described in comparison to the origin of the original “discovery” study population. In addition, requests should address the power of the replication sample set to detect a smaller genetic effect than reported in the original study in order to address potential publication bias and the “winner’s curse” phenomenon. Budget requests must not exceed $400,000 in total costs for a funding period not exceeding 12 months.
Submission of Requests
Requests for these administrative supplements must be submitted by May 1, 2008.
Please note that the NIH Center for Scientific Review (CSR) IS NOT involved in receipt and processing of these requests. The NCI will receive these administrative supplement requests.
Please submit a signed original of the request and five signed, single-sided photocopies, in one package to:
Elizabeth Gillanders, Ph.D.
Epidemiology and Genetics Research Program
Division of Cancer Control and Population Sciences
National Cancer Institute
6130 Executive Boulevard, EPN Room 5140, MSC 7324
Bethesda, MD 20892-0001 (for U.S. Postal Service express or regular mail)
Rockville, MD 20852 (for non-USPS delivery)
Telephone: 301-594-5868
E-mail: [email protected]
Evaluation of Requests
NIH program staff members (and appropriate outside consultants) who have expertise in genetic association studies, as well as the proposed phenotypes will evaluate requests. Awards will be determined on the basis of scientific merit, programmatic priorities as noted above, programmatic balance and availability of funds.
The earliest anticipated award date for this program will be September 1, 2008.
Inquiries
General inquiries concerning the programmatic and review matters should be directed to:
Elizabeth Gillanders, Ph.D.
(see contact information above)
Inquiries regarding administrative and fiscal matters should be directed to:
Crystal Wolfrey
Office of Grants Administration
National Cancer Institute
6120 Executive Boulevard, EPS Room 243, MSC 7150
Bethesda, MD 20892-7150 (for U.S. Postal Service express or regular mail)
Rockville, MD 20852 (for non-USPS delivery)
Telephone: 301-496-8634
E-mail: [email protected]
and Human Services (HHS)
