Genomic Research in Preventing and Treating Heart, Lung, and Blood Diseases

April 9 - 10 , 2014
Bethesda, MD


Since 2007, genome-wide association studies (GWAS) have identified more than one thousand genomic regions associated with heart, lung, blood, and sleep (HLBS) diseases. Researchers now have the opportunity to explore these genomic regions more easily because of advances in DNA sequencing and the resulting lower cost of whole genome sequencing (WGS). Sequencing studies can reveal critical genetic variants, and follow-up investigations can characterize the variants’ biological functions and evaluate the variants’ clinical implications. As these studies proceed, new technologies are changing health care: mobile technologies have created new ways to monitor health, and electronic health records (EHRs) and cloud computing are enabling large-scale studies.  The emergence of this wealth of patient-derived data and genomic information represents an unprecedented opportunity to translate genomic research into clinical practice as the NHLBI community transitions toward precision medicine for HLBS disorders.


To determine how to leverage these innovations to improve our understanding and treatment of HLBS diseases, the National Heart, Lung, and Blood Institute (NHLBI) convened a workshop of multidisciplinary researchers on April 9 and 10, 2014, in Bethesda, MD. The main goals of the workshop were as follows:

  1. To determine how to best utilize NHLBI’s population and clinical cohort studies, associated omics programs, and new infrastructure that researchers are creating under trans-NIH initiatives to advance opportunities and priorities in precision medicine.
  2. To assess how the NHLBI can augment its clinical and population-based epidemiological studies by employing electronic health records, developing standardized data and sample collection procedures, and adding new tools for clinical measurements, including mobile and point-of-care devices.
  3. To identify research gaps and potential solutions to advance the translation of basic genomics findings into precision medicine and public health approaches.
  4. To outline specific steps over the next five years that could contribute to the achievement of these goals.


NHLBI Working Group

Genetics and Genomic Medicine Working Group

The Future of Genomic Research for Prevention and Treatment of Heart, Lung, and Blood Diseases Executive Summary


Workshop participants recommended that the following actions be explored:

  1. Establishment of a WGS project

    1. Implementation of a WGS project would involve several phases. i.
      1. In Phase 1 researchers would begin to create a large-scale genomic resource by sequencing the genomes of a diverse sample of approximately 70,000 well-characterized participants as well as collecting other omics data (e.g., RNA sequences and metabolite information). This novel, large-scale, multi-omic resource with well phenotyped participants will provide the community with a platform to elucidate the molecular pathways associated with HLBS phenotypes in health and disease. This phase could take place within the next five years and would include analyses focused on major HLBS diseases. ii.
      2. In Phase 2 researchers would perform additional whole-genome sequencing of different patient sub-sets that would build upon this initial consortium cohort.. During this phase, researchers could determine whether there is a correlation between particular genetic factors and the patient’s clinical outcome, or response to a drug and whether there is a link between specific genes and extreme responses to environmental changes, such as dietary changes.
    2. Collaborations with other NIH institutes, such as NHGRI, and other Federal agencies and health systems will be helpful for the success of the WGS project and its sustainability.
    3. The WGS project will derive great benefit if the analyzes of DNA samples from a diverse number of sources, including ancestral groups currently under-represented in domestic genomic resources, patients within large primary health care system networks, individuals from family studies, and patients who are part of existing well-characterized cohort studies. Whole-genome sequencing of individuals from family studies may be particularly beneficial because the genetic variants identified through pedigree-based analyses are typically more statistically reliable. The WGS program could also be used to support the training and career development of the next generation of genomic investigators in HLBS disorders.
  2. Support of functional studies of disease-associated genetic variants
    1. The following actions might prove beneficial in carrying out such studies:
      1. Development of state-of-the-art high-throughput methods for analyzing the function of coding and non-coding variants in genes that mediate HLBS phenotypes.
      2. Establish a high-resolution genomic resource of human DNA variation at loci associated HLBS disorders in large-scale ‘meta-cohort’ of individuals with in-depth HLBS phenotype characterization.
      3. The selection of traits that are inherited to identify their underlying genetic variants in both regions of the genome that code for proteins and those that do not.
      4. The promotion of integrative omics approaches (genome, epigenome, transcriptome, proteome, metabolome) to study the differences between health and disease for HLBS disorders.
      5. The funding of studies that characterize so-called natural knockouts, which are individuals for whom a gene is mutated and does not produce a functional protein (so that in effect the gene has been knocked out). Studying well phenotyped individuals with ‘knockout mutations’ could provide important insights into the impact of a protein’s absence on human health and disease.
      6. The characterization of individuals who appear to be naturally protected from a particular HLBS disorder. For example, an individual may engage in behaviors that would put most people at risk for cardiovascular disease but nevertheless have arteries that show minimal plaque accumulation. Studying such individuals may enable researchers to identify genetic elements, such as super-resilience genetic variants, that explain these individuals’ natural protection from a disease. Once researchers identify the source of the protection, they might also be able to develop novel therapeutic strategies that recapitulate the protection in patients who naturally lack the genetic variants associated with resilience.
  3. Development of clinical applications of basic research findings
    1. Providing support for researchers that explore the utility of applying genomic information in clinical practice based on the evidence from clinical trials that incorporate genomic data in the study design. This program would begin to create the basis for Precision Medicine Clinical Trials that target therapeutic interventions to specific sub-sets of patients based on genomic information.
    2. Establishment of a research portfolio of exposure biomarkers as indicators for environmental and other physiologic disturbances as well as gene-environment interactions might prove beneficial. This program would begin to support the evaluation of gene-environment interactions and the epigenome in HLBS phenotypes.
    3. Organization of clinical studies into networks for biomarker discovery and testing could be considered. This biomarker discovery network could include multiple hubs, each devoted to a particular type or group of conditions and each collecting biospecimen.
  4. Establishment of a scientific/data commons with a web portal
    1. A data commons and web-portal could be created that integrated information from EHRs, omics studies, biosensors, health-monitoring apps, geo-spatial apps, and environmental monitors (such as air quality monitors), thereby enabling researchers to make connections between the various elements. For example, investigators could correlate asthma drug prescription rates in a particular region with air quality.
    2. This resource should align with NIH data-sharing policies to ensure the appropriate balance of data accessibility with safeguards for data integrity and privacy protection of participants.
    3. Information technology programs could also be created that enable the analysis of this data.
    4. This resource could provide tremendous new training opportunities for the NHLBI community as well as attract investigators from other disciples (e.g. data sciences, computational biology) to study HLBS disorders.

Planning Organizing Committee (POC):

  • Eric Boerwinkle, Ph.D., University of Texas Health Science Center
  • Geoffrey S. Ginsburg, M.D., Ph.D., Duke University
  • Isaac S. Kohane M.D., Ph.D., Harvard Medical School
  • Bruce M. Psaty, M.D., Ph.D., University of Washington
  • Gary H. Gibbons, M.D., National Heart, Lung, and Blood Institute, NIH (Ex officio)
  • Cashell E. Jaquish, Ph.D., National Heart, Lung, and Blood Institute, NIH
  • Jennie Larkin, Ph.D., National Heart, Lung, and Blood Institute, NIH
  • Alan M. Michelson, M.D., Ph.D. National Heart, Lung and Blood Institute, NIH (POC Co-Chair)
  • Christopher O’Donnell, M.D., M.P.H., National Heart, Lung and Blood Institute, NIH (POC Co-Chair)


  • David Carrell, Ph.D., Group Health Research Institute
  • Aravinda Chakravarti, Ph.D., Johns Hopkins
  • Richard Cooper, M.D., Loyola University Chicago L.
  • Adrienne Cupples, Ph.D., Boston University
  • Ronald G. Crystal, M.D., Weill Cornell Medical College
  • Matthew S. Freiberg, M.D. MS.c., University of Pittsburg
  • Stephen Friend, M.D., Ph.D., Sage Bionetworks
  • Michael Gaziano, M.D., Harvard Medical School
  • David Ginsburg, M.D., University of Michigan
  • Mark Guyer, Ph.D., National Human Genome Research Institute, NIH
  • David Ledbetter, Ph.D., Genomic Medicine Institute
  • Sandra Soo-Jin Lee, Ph.D., Stanford University
  • Daniel Levy, M.D., National Heart Lung and Blood Institute, NIH
  • Stephanie London, M.D., Dr.P.H., National Institute of Environmental Health Sciences, NIH
  • Deborah Nickerson, Ph.D., University of Washington
  • Dan L. Nicolae, Ph.D., University of Chicago
  • Peipei Ping, Ph.D., University of California, Los Angeles
  • Daniel Rader, M.D., University of Pennsylvania
  • Susan Redline, M.D., M.P.H., Harvard Medical School
  • Stephen Rich, Ph.D., University of Virginia School of Medicine
  • Neil Risch, Ph.D., University of California, San Francisco
  • Dan Roden, M.D., Vanderbilt University Medical Center
  • Charles N. Rotimi, Ph.D., National Human Genome Research Institute, NIH
  • Edwin K. Silverman, M.D., Ph.D., Brigham and Women’s Hospital / Harvard Medical School
  • John A. Stamatoyannopoulos, M.D., University of Washington
  • Russell Tracy, Ph.D., University of Vermont
  • Russell E. Ware, M.D., Ph.D., Cincinnati Children’s Hospital Medical Center
  • Deborah Applebaum-Bowden, National Heart, Lung, and Blood Institute, NIH
  • Weiniu Gan, Ph.D., National Heart, Lung, and Blood Institute, NIH
  • James Kiley, Ph.D., National Heart, Lung, and Blood Institute, NIH
  • Pankaj Qasba, National Heart, Lung, and Blood Institute, NIH
  • Philip Bourne, Ph.D., NIH