Request for Information: NHLBI Whole Genome Sequencing Project (NHLBI-WGS)

Notice Number: NOT-HL-14-030

Key Dates
Release Date: July 17, 2014
Response Date: August 1, 2014

Related Announcements

Update: The following update relating to this announcement has been issued:

Issued by
National Heart, Lung, and Blood Institute (NHLBI)


The National Heart, Lung, and Blood Institute (NHLBI) is seeking information regarding existing studies (including but not limited to families, founder populations, population isolates, clinical studies and cohorts) with available biospecimens that may be suitable for Whole Genome Sequencing (WGS) and RNA sequencing to discover genetic variants influencing complex traits and diseases relevant to NHLBI’s mission.  The NHLBI especially seeks information about studies of traditionally underrepresented populations and those with high impact heart, lung, blood (HLB) phenotypes or disorders.

Background Information

The NHLBI has made an early and large investment in the application of genetic and genomic technology to understanding the underlying etiology of heart, lung and blood disorders.  The investment has included family-based cohorts and founder populations that have been used successfully for gene discovery by relying on the concepts of heritability and differential transmission of disease susceptibility alleles, as well as large well-phenotyped cohorts and consortia that were used successfully in Genome Wide Association Studies (GWAS) where large sample sizes are necessary for association studies.

NHLBI believes that considerable value to the scientific community will be added to these cohorts by making genome sequence data available for them, within the context of an appropriate project design. The NHLBI seeks to pursue this to discover genetic variants influencing heart, lung, and blood disorders in multiple ethnic groups.  WGS is proposed here because it allows analysis of noncoding variants and is increasingly economically feasible at a scale of tens of thousands of individuals, providing sufficient statistical power for these studies.

It is important to note that there is still relatively limited genomic information from non-European ancestry groups.  There is an opportunity to bridge this gap within the context of the project designs contemplated here (family-based, founder populations, case-control, etc.), with the idea that a good design will aid discovery of variants that will be generally informative about the biology of HLB disease across groups and may be informative about differences in disease prevalence among groups.  WGS coupled with other -omic methods such as RNAseq and existing phenotype and outcome data will provide a wealth of information to aid in unraveling the underlying contributors to HLB disease.  Ultimately, NHLBI will build a data commons to integrate this genome sequence, other -omic data, and clinical data as a common resource for the scientific community.

A webpage for frequently asked questions is available at:

Information Requested

The NHLBI seeks information regarding the availability of studies with sample sets of European and non-European origin for a WGS project.  Sample sets should afford sufficient statistical power to allow detection of novel variants of small effect on complex diseases and phenotypes of high importance to NHLBI in the context of a WGS study.  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.  Studies should have a design and existing genotyping data to allow imputation to large numbers of samples based on deep sequencing on a limited number of informative members.  Family based study designs should include information about appropriate information about pedigree structure and ascertainment.  Case-control designs should include information about case definition and control matching.  Samples, and associated data should be available and transferrable.  Participants should have been consented for data sharing, WGS, and multi-use (ability to perform analysis of multiple traits and measures, not just one single disease). 

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

  1. The optimal study design and sample size for a WGS project using the samples. Information on minimal samples sizes, case-control definition, family structure, optimal family member sampling/inclusion, and statistical power can be included.
  2. The availability of study data and samples (include sample sizes, availability, including amount of high quality DNA and RNA) with the above design who are of African Ancestry, American Continental Ancestry (Natives of North and South America), European Ancestry, and/or Other Ancestry (e.g. Asiatic, Pacific Islander, Aboriginal, etc.)
  3. The identification of important phenotypes or common disorders where WGS can contribute significant knowledge to the underlying biology/etiology in each of these ancestral groups.
  4. The opportunities for replication of findings from the proposed study/ethnic group(s).
  5. The barriers (if any) to sharing WGS data from above cited studies in dbGAP. Your comments can include options in data sharing that may help to overcome these barriers.
  6. Most recent publications and/or websites that provide more comprehensive details of the populations. When possible, include relevant PMIDs.


All responses must be submitted via email to by August 1, 2014. Please include the Notice number NOT-HL-14-030 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, 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:

Cashell Jaquish, Ph.D
Division of Cardiovascular Sciences
National Heart Lung and Blood Institute (NHLBI)
Telephone:  301-435-0447

Weiniu Gan, Ph.D.
Division of Lung Diseases
National Heart, Lung and Blood Institute (NHLBI)
Telephone:  301-435-0202

Pankaj Qasba, PhD
Division of Blood Diseases and Resources
National Heart Lung and Blood Institute (NHLBI)
Telephone:  301-435-0050