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Frequently Asked Questions About RFA-HG-06-033

Frequently Asked Questions About RFA-HG-06-033

Genome-Wide Association Studies in the Genes, Environment and Health Initiative Study Investigators

October 25, 2006
Revised November 15, 2006

Is the Genes, Environment and Health Initiative (GEI) focusing on specific diseases?

The Genes, Environment and Health Initiative (GEI) is an NIH-wide initiative. We hope to receive applications that address a diverse set of conditions and traits of public health importance. The examples in the RFA do not imply a higher priority for any of the listed conditions or traits.

Are GWA studies submitted to GEI required to have measures of environmental exposures?

No. Availability of environmental exposures is not required, but will be considered as one of many factors in the evaluation and award process. Because of the connection of the GEI-GWA program with the GEI Exposure Biology Program, higher priority will be given to selecting studies that have evidence for environmental influences on the trait, high-quality data on environmental exposures, and stored biospecimens. Other factors, as outlined in the RFA, will also be considered (public health significance, programmatic balance, population diversity, quality and ease-of-use of the dataset, and quality and quantity of DNA).

What kind of exposures are you planning to study? Are you only focusing on environmental exposures such as toxins?

The most important exposures in any given study are those relevant to the condition or trait that is under investigation, particularly if they might be expected to modify the effect of genetic variants identified through the genome-wide association studies conducted in GEI.

GEI is intended to examine a wide range of exposures, including lifestyle factors such as smoking, physical activity, or diet, and exposures in the environment such as air pollution or pesticides. These examples and those in the RFA do not imply a higher priority for particular types of exposure.

GEI is also intended to examine conditions or questions that include defined exposures such as those involved in infectious diseases and pharmacogenomics.

Can measurements of environment exposures be made on biospecimens?

This RFA will not fund additional measurements. There may be other opportunities within the GEI program for doing such measurements. The availability of stored biospecimens for future analysis is highly desirable and should be described in your application.

If such measurements are done outside of GEI and you wish to share them through the GEI program, you may send the information to NCBI to link to the rest of your study's data.

Who will do the genotyping?

The Genotyping Facilities selected competitively through RFA-HG-06-014 - Genome-wide Association Studies in the Genes and Environment Initiative - Genotyping Facilities [grants.nih.gov] - will provide genotyping services.

What genotyping platforms will be used?

We don't know what genotyping platforms will be used. Genotyping Facility applications will be reviewed in the same timeframe as Study Investigator applications. The requirement is that proposed platforms should provide at least 80 percent coverage of human genomic variation.

Should the genotyping costs be included in my budget?

Genotyping costs should NOT be included in the Study Investigator application. Those costs will be included in the Genotyping Facilities' budgets.

Genotyping Facilities will be able to extract DNA or perform genome-wide amplification if necessary, so those costs do not have to be included in the Study Investigator budget either.

Are fine-mapping studies within the scope of this RFA?

Although the focus of this RFA is on initial genome-wide scanning and replication studies, fine-mapping studies may be proposed under this RFA. Genotyping for each study will be performed by one of the GEI Genotyping Facilities selected competitively through RFA-HG-06-014 - Genome-wide Association Studies in the Genes and Environment Initiative - Genotyping Facilities [grants.nih.gov]. It may be helpful to review that RFA to better understand the expectations for Genotyping Facilities.

Are sequencing and functional studies within the scope of this RFA?

No. Only genotyping is within the scope of this RFA. Genotyping for each study will be performed by one of the GEI Genotyping Facilities selected competitively through RFA-HG-06-014: Genome-wide Association Studies in the Genes and Environment Initiative - Genotyping Facilities [grants.nih.gov].

Sequencing and functional studies are within the scope of GEI generally. There may be other opportunities within GEI to apply for support for sequencing and functional studies.

How will NCBI share study data with investigators?

The current plan is for NCBI to provide to Study Investigators, and all others whose requests are approved by the Data Access Committee, a secure method for downloading the requested GEI study dataset. There is no current plan to provide analytic capabilities to investigators through NCBI's Web site or at NCBI. Thus, investigators will not be able to conduct analyses without obtaining a copy of the requested dataset.

NCBI will perform basic genotype-phenotype correlations, the results of which will be provided through NCBI's Web site.

NIH has issued a Request for Information (RFI) related to data-sharing for genome-wide association studies (Proposed Policy for Sharing of Data obtained in NIH supported or conducted Genome-Wide Association Studies); the deadline for comments is November 30, 2006 (Extended Comment Period for the Proposed Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies). We expect that the policy will be finalized prior to the initiation of GEI-GWA studies. Final GEI data-sharing policies will be consistent with NIH-wide data-sharing policies or guidelines for genome-wide association studies.

What is the Study Investigator's role in data analysis, as distinguished from the Coordinating Center's role?

Study Investigators will have primary responsibility for analyzing genotype and phenotype data from their own study, but may request assistance from the Coordinating Center if desired. The Coordinating Center will be responsible for cross-study functions, such as harmonizing data across studies and leading any cross-study analyses in collaboration with the Study Investigators and NIH staff. The Coordinating Center may provide support to Study Investigators for analyses if desired and as funding permits.

As described in the RFAs, applications for both the Coordinating Center - Genome-Wide Association Studies in the Genes and Environment Initiative - Coordinating Centers [grants.nih.gov] - and for the Study Investigators - Genome-Wide Association Studies in the Genes and Environment Initiative - Study Investigators [grants.nih.gov] will be evaluated for the quality of their data analysis plans and expertise, recognizing their respective roles (leadership, supporting, individual study, cross-study, etc).

Will funding be available to support data and specimen submission that is part of the application process (e.g., pre-award analysis of DNA quality and quantity for a sample of specimens, as specified in the RFA)?

No. Funding will not be available for pre-award activities.

How much DNA will be needed for the genome-wide genotyping?

We anticipate that at least 5 micrograms of DNA will be needed for the genome-wide genotyping, although this amount might require whole genome amplification before genotyping. Applicants should be aware that some platforms require as much as 20-50 micrograms per sample to avoid whole genome amplification. However, minimum DNA quantity differs across genotyping platforms and we don't know yet what platforms will be selected. Genotyping Facility applications will be reviewed in the same timeframe as Study Investigator applications.

Can whole genome amplification be done? Can DNA extraction be done?

Yes. We anticipate that the Genotyping Facilities will have the capability to perform whole genome amplification and DNA extraction.

Who will clean the genotyping data?

The National Center for Biotechnology Information (NCBI) will work with the Genotyping Facilities and Study Investigators to resolve any issues with the genotyping data, and link those data to the phenotype and risk factor information.

What genotyping data will be available to investigators?

The Genotyping Facilities will provide genotyping assays, genotype calls, quality scores, and .cel files (or equivalent). All data, both good and bad, will be released with the bad data flagged.

My Institutional Review Board (IRB) approved submission of study data and specimens for inclusion in GEI and broad data-sharing. What are you looking for in the study consent forms and process?

We will look for some of the same things that an IRB might look for. Specific elements:

  • Is there a statement that data or specimens may be shared with other researchers for future research?
  • Is it clear that the study may include future genetic research?
  • Is there a statement that data or specimens will not be shared, or that the research will be conducted only in specific laboratories or institutions? (This would preclude inclusion in GEI without additional consent from participants.)

We will also look for limitations on use of the data, such as:

  • Use limited to research on a specific disease or condition.
  • Exclusion of commercial uses.
  • IRB approval required for every use of the data.

While these limitations will not exclude an application from being considered responsive, they will be considered in the evaluation and award process.

Procedures for individual participant withdrawal from the study that are inconsistent with the proposed data-sharing policies and procedures may preclude inclusion in GEI. This will be evaluated on a case-by-case basis.

We recognize that applications may be based on study data for which consent was obtained years ago, before genome-wide genotyping and broad data-sharing may have been considered in the consent process. If you or your IRB are concerned that consent was not adequate for the proposed GEI GWA study, you may include a plan, timeline, and budget estimates for reconsent as part of your application.

Last updated: March 07, 2012