Request for Information: Samples for Comprehensive Studies of Genome Sequence Variation Underlying Common Disease

Notice Number:


Key Dates

Release Date: December 11, 2014

Response date: New Date January 15, 2015 per NOT-HG-15-012. December 31, 2014

Related Announcements



Issued by

National Human Genome Research Institute (NHGRI)


The National Human Genome Research Institute (NHGRI) intends to publish a Request for Applications soliciting Centers for Common Disease Genomics (see related announcement above), whose purpose will be to undertake large, comprehensive genome sequencing studies to identify and characterize variants underlying a range of common, complex human diseases. The general goals of the planned program follow from discussions at an NHGRI Workshop on the Future of Genome Sequencing (, and a Concept for an initiative has been approved by the National Advisory Council for Human Genome Research (see Briefly, the approved Concept envisions an effort that will pursue multiple common disease projects that cover a range of different presumed genomic architectures and study designs, and that will be as comprehensive as possible with respect to study power, ability to analyze both coding and noncoding regions, and other factors.

Some of the discussions on this topic have centered on the availability of sufficient numbers of well-characterized and appropriately consented human samples that could potentially be employed for such an effort, considering both the need to attain adequate power to detect variants of relatively small effect size and/or low population frequency. Large sample numbers are likely to be required for well-powered genome sequencing studies of common disease, potentially in the tens of thousands, particularly if noncoding sequence is to be analyzed. NHGRI is aware that other NIH Institutes, and other funders, have significant previous and ongoing investments in large genomics studies, especially Genome Wide Association Studies (GWAS), which have included tens of thousands of samples for a number of common disease phenotypes. Other considerations in selecting common disease sample sets for study may include: genetic architecture and public health importance of the disease; ancestral diversity of the sample set; ready availability of samples; adequacy of consent for wide data sharing; potential ability to return incidental findings; potential for identifying additional causative variants, elucidating gene function, and identifying therapeutic targets; and presence of a strong and committed funding partner such as another NIH Institute or Center.

Information Requested

This RFI seeks information from the community about the availability, quality, diversity, and degree of characterization of human samples that could potentially be used for comprehensive sequencing studies to understand the genomic architecture of common disease. Sample sets should afford sufficient statistical power to allow detection of novel variants of small effect on complex diseases and phenotypes of high significance for human health. Such samples should already be part of an ongoing study; studies should have multiple phenotypes previously measured, proven high quality DNA and may have been ascertained at random or by disease status. Family based study designs should include information about what pedigree structure and ascertainment may be available. Case-control designs should include information about case definition and control matching; for case-control designs we particularly seek information about larger sample sets (>5000). Samples, and associated data should be available and transferrable. Participants should have been consented for data sharing, genome sequencing, and multi-use (ability to perform analysis of multiple traits and measures, not just one single disease).

The NHGRI seeks comments on any or all of the following topics, but not limited to:

  1. Number of samples for a particular common disease phenotype. Information about ancestry, continental and/or aboriginal ancestry can be included;
  2. Availability of samples from specific populations that for scientific reasons may be highly desirable;
  3. The availability of high-quality phenotypic characterization;
  4. The availability of information about the amount of genomic DNA that would be available per sample.
  5. Availability, format, and organization of samples and existing data about samples;
  6. Availability of other information about samples that may be relevant for follow-on studies proximate to genomic sequencing, for example exposure data or availability of tissues or ability to re-contact participants;
  7. Barriers, if any, to sharing sequence data in dbGaP from the specific studies.
  8. Opportunities that the availability of sequence data will create for those that may have an interest in the samples and the sequence data including the ability of the community to take advantage of those opportunities, or use in previous studies;
  9. Types of epidemiological study designs that the samples have been, or are being, used for, and potential genome sequencing study designs for which the samples could be suitable;
  10. Information about any recent publications that include details about the sample sets being described.

Respondents are encouraged to include any other discussion about criteria that should be considered for including sample sets in large, comprehensive genome sequencing studies seeking to identify and characterize rare variants influencing common, complex human diseases.

Given the questions above, NHGRI believes that effective responses to this RFI are most likely to come from communities/consortia working on large projects in the genomics of particular common human disease, or individuals who are closely familiar with consortia who have already needed to coordinate across studies in order to attain large sample numbers for scientific reasons.


All responses must be submitted via email to by January 15, 2015. Please include the Notice number NOT-HG-15-007 in the subject line. Response to this RFI is voluntary. Responders are free to address any or all of the categories listed above.

This RFI is for planning purposes only and should not be construed as a solicitation for applications or as an obligation on the part of the Government to provide support for any ideas identified in response to it. Please note that the United States Government will not pay for the preparation of any information submitted or for its use of that information.

Responses will be compiled and shared internally and with working groups convened by the NIH, as appropriate. In all cases where responses are shared, unless the respondent indicates otherwise, the names of the respondents will be withheld. We look forward to your input and hope that you will share this document with your colleagues.


Please direct all inquiries to:

Adam Felsenfeld, Ph.D.
National Human Genome Research Institute (NHGRI)
Telephone: 301-435-5539