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Genomic Variation Identification, Association and Function in Human Health

Event Details

Participants will help NHGRI develop a 5-10 year strategy to advance our ability to find and characterize genomic variants, the genomic elements in which they reside or that they affect and understand the effects of those variants on human health and disease.

We seek recommendations for projects, community resources, knowledge, and research directions that NHGRI should pursue, as well as consideration of key ongoing efforts that should be continued or revised. We also seek recommendations for mid-scale projects that could be initiated in the next year (e.g.,, ideas that build on the ENCODE Project and the Genome Sequencing Programs) and long-term projects that may require pilot projects, development of technologies or resources and establishment of collaborations.


Hilton Washington, D.C.
Rockville Hotel & Executive Meeting Center
Plaza Ballroom


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Relating genomic variation to human phenotype is a central issue in genomics.

There are several ways to consider this problem, but the elements are: identifying genomic variants; associating them with regulatory elements, genes and phenotypes; and understanding gene, regulatory element and variant function. Within this, or added to it, would be an understanding of epistasis and environmental influences on genotype.

There are now many individual examples (genes/phenotypes) where we have a reasonably detailed understanding of the relationship between variant and disease- these have defined the paradigm. But these so far mostly represent simpler cases: Mendelian (i.e., very strong effect) traits; diseases where the physiology is straightforward (e.g., inborn errors of metabolism); and some cancers.

But the aim of human genomics is to solve this problem at scale for all human traits that have an inherited component, and in so doing, gain biological insight into the nature of inherited disease, insight into mechanisms of variant, regulatory element and gene function, and ultimately to provide a rational foundation for clinical applications. To develop approaches to do this, NHGRI seeks to understand the state-of-the-art, gaps in the field (knowledge, methods, data and resources), find better ways to integrate the information from the separate elements, and identify promising new approaches to address the general problem.

This workshop is one of a series of activities devoted to strategic planning for NHGRI. The recommendations forthcoming from the workshop discussions will inform the NHGRI "2020 Vision for Genomics" Strategic Planning efforts.

Workshop Topics

The workshop is divided into four parts:

  1. Setting the Stage: "Vision" discussions to imagine what the field can (or must) be a decade from now.
  2. Scientific Issues: The current state-of-the-art to identify challenges and opportunities:
    • Day 1: variant discovery and association with traits
    • Day 2: functional element discovery and characterization, and the interpretation of how variants effect function
    • Breakout sessions will extend the discussions, raising specific examples that NHGRI could pursue (e.g., specific projects, methods, knowledge, resources, data, etc.)
  3. What should NHGRI do?: Integration of the recommendations from the preceding days; placing them in a wider context; identifying specific things NHGRI should do.
  4. Synthesis and Prioritization: Prioritization among the projects, directions, resources, etc. recommended during the workshop.

Workshop Sessions

  • Tuesday, January 22, 2019
  • 8:00 - 8:30 a.m. Registration
  • 8:30 - 8:40 a.m. Welcome and Introduction
    Eric Green
  • 8:40 - 9:00 a.m. Statement of Meeting Goals
    Elise Feingold
    Adam Felsenfeld
  • Part I: Setting the Stage Visions of the Future: What will the field of genomics look like in 5-10 years? How will it get there?
  • 9:00 - 9:15 a.m. Vision Talk 1
    Jay Shendure
  • 9:15 - 9:30 a.m. Vision Talk 2
    Judy Cho
  • 9:30 - 9:45 a.m. Vision Talk 3
    Emma Farley
  • 9:45 - 10:45 a.m. Discussion
    John Stamatoyannopoulos
    Heidi Rehm
    Tuuli Lapplainen
  • Part II: Scientific Issues
  • 11:00 - 11:05 a.m. Deliverables for Part II
    NHGRI Staff
    Meeting Advisors
  • 11:05 - 11:25 a.m. NHGRI's Current Approach to "Variant to Function to Disease"
    NHGRI Staff
  • 11:25 - 12:10 p.m. Current State of the Art in Variant Discovery and Association
    Amit Khera
    Laura Bierut
    Jonathan Haines
  • 12:10 - 12:55 p.m. Moderated Discussion
    Gonçalo Abecasis

    How should NHGRI approach these scientific issues in the future?
    What are the important questions to ask?
    Where and how will NHGRI get samples/data?
  • 2:00 - 2:15 p.m. Breakout Session Charge   
    NHGRI Staff
    Meeting Advisors
  • 2:15 - 3:15 p.m. Day 1 Breakout Sessions (concurrent)

    Breakout 1 
    (Roosevelt Room)
    How much more sequencing, if any, is needed to study Mendelian and common disease, and what should NHGRI do in this area? Why?
    Eric Boerwinkle
    Nancy Cox

    Breakout 2 (Madison Room)
    How and why to approach structural variation and other "hard to measure" variation?
    Charles Lee
    Karen Miga

    Breakout 3 (Jefferson Room)
    How and why to approach more complex features- e.g., GxE, epistasis?
    Andrew Clark
    Eimear Kenny
  • 3:45 - 5:15 p.m. Breakout Summaries and Discussion
    Breakout Session Co-Chairs
    Moderator: Lon Cardon
  • 5:15 - 5:30 p.m. Summation of Day 1 and Prep for Day 2
  • 5:30 p.m. Group Photo


  • Wednesday, January 23, 2019
  • 8:00 - 8:15 a.m. Introduction: Variant and Genome Function
    NHGRI Staff
  • 8:15 - 9:00 a.m. Current State of the Art: Functional Data, Analysis and Interpretation
    Hugo Bellen
    Lea Starita
    Timothy Reddy
  • 9:00 - 10:00 a.m. Moderated Discussion
    Brenton Graveley

    How should we be doing this into the future?
    What resources, new technologies and computational capabilities do we need to generate and make use of functional data?
    What is needed to overcome barriers to performing functional studies at scale?
  • 10:15 - 10:30 a.m Breakout Session Charge
    NHGRI Staff
    Meeting Advisors
  • 10:30 - 11:30 a.m. Day 2 Breakout Sessions (concurrent)

    Breakout 4 
    (Roosevelt Room)
    Identification and characterization of all genes and regulatory elements
    Kelly Frazer
    Wendy Chung

    Breakout 5 (Madison Room)
    Determining the functional consequences of variants acting individually and in combination
    Kelly Frazer
    Wendy Chung

    Breakout (Jefferson Room)
    Accurate prediction of the regulatory consequences of variants, and modeling gene regulation
    Trey Ideker
    Christina Leslie
  • 12:30 - 2:00 p.m. Breakout Reports and Discussion
    Breakout Session Co-Chairs
    Moderator: Joseph Ecker
  • 2:15 - 3:00 p.m. Focus Discussion 1
    Len Pennacchio
    Barbara Wold
    Andrea Califano

    What can NHGRI do to facilitate bridging molecular and organismal phenotype?
  • 3:00 - 3:45 p.m. Focus Discussion 2
    Richard Myers
    Katherine Pollard
    Daniele Fallin

    Bridging Day 1 and Day 2: Connecting discussions about variation, function and phenotype
  • Part III: What should NHGRI do?
  • 3:45 - 4:00 p.m. Brief recap of Part III deliverables: Brainstorming for NHGRI-supported Activities
    NHGRI Staff
    Meeting Advisors
  • How to Achieve the Science - Four Topics (below)
    What can NHGRI do to address the major recommendations?
    What insights, capabilities, policies, initiatives, collaborations, alliances, etc. should we pursue?
  • 4:00 - 4:45 p.m Topic 1: Discovery and Interpretation of Variation Associated with Human Health and Disease

    Barbara Stranger
    Anshul Kundaje
    David Valle

    Michael Boehnke

  • 4:45 - 5:30 p.m. Topic 3:  Predicting and Characterizing Functional Consequences of Genome Variation, Including Beyond Single Variant/Gene

    Nadav Ahituv
    Dana Crawford
    Neville Sanjana

    Jonathan Pritchard


  • Thursday, January 24, 2019
  • 8:00 - 8:15 a.m. Day 3: Introduction
    NHGRI Staff
  • 8:15 - 9:00 a.m. Topic 4: Data Resources, Methods, Technologies and Computational Capabilities

    Christina Leslie
    Marylyn Ritchie
    Jason Buenrostro

    Aviv Regev

  • 9:00 - 9:45 a.m. Topic 2: Addressing Basic Research Questions that Anticipate Clinical Needs

    Howard Chang
    Stephen Chanock
    Howard Jacob

    Sharon Plon

  • Part IV: Synthesis and Prioritization
  • 10:15 - 12:15 p.m. Recommendations for NHGRI Priorities

    Meeting Co-chairs & 
    Meeting Advisors:
    Jay Shendure
    Joseph Ecker
    Sharon Plon
    Katherine Pollard

    Moderated discussion on future NHGRI priorities for specific initiatives, data sets, knowledge, capabilities
  • 12:15 - 1:00 p.m. Summation of the Meeting
    NHGRI Staff
  • End of Main Meeting
  • 1:00 - 3:00 p.m.  Working Lunch/NHGRI and Advisors
    NHGRI Staff
    Meeting Advisors

Last updated: February 4, 2019