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On September 12-13, 2012, the National Human Genome Research Institute (NHGRI), sponsored a workshop - Implicating Sequence Variants in Human Disease - at the Hyatt Regency Bethesda, in Bethesda, Md. Teri Manolio, M.D., Ph.D., NHGRI, and Daniel MacArthur, Ph.D., Massachusetts General Hospital, co-chaired the workshop. The goal of the workshop was to develop guidelines for investigators, reviewers and editors to consider in assessing the evidence implicating sequence variants or genes as causal in a specific disease.


Wednesday, September 12, 2012

  Topic Speaker
1 Welcome and Introductions
Daniel MacArthur, Ph.D.
Massachusetts General Hospital
2 The Need for Criteria to Implicate DNA Variants: Real-World Examples
Video | Slides
Mark Daly, Ph.D.
Massachusetts General Hospital
3 Maintaining Accurate Information in Variant Databases
Video | Slides
Heidi Rehm, Ph.D., F.A.C.M.G
Partners Healthcare
4 Laboratory Perspectives on Variant Implication David Dimmock, M.D.
Medical College of Wisconsin
5 Discussion
All Participants


Thursday, September 13, 2012

  Topic Speaker
6 Revisions (as needed) to Plans for Day's Discussions
Daniel MacArthur, Ph.D.
Massachusetts General Hospital
7 Study Design: What sample selection and data processing procedures maximize power and minimize false positives in identifying causal variants?
Video | Slides
Study Design Workgroup:
  • Jeffrey Barrett, Ph.D.
  • Nancy Cox, Ph.D.
  • Teri Manolio, M.D., Ph.D.
  • Benjamin Voight, Ph.D.
8 Statistical Analysis: How can we robustly identify variants underlying disease?
Video | Slides
Statistical Analysis Workgroup:
  • Suzanne Leal, Ph.D.
  • Goncalo Abecasis, D.Phil.
  • Joel Hirschhorn, M.D., Ph.D.
  • Daniel MacArthur, Ph.D
9 Known Variants: Which candidate causal variants/genes in a patient or cohort have been previously implicated in similar phenotypes?
Video | Slides
Known Variants Workgroup:
  • David Goldstein, Ph.D.
  • Russ Altman, M.D., Ph.D.
  • Leslie Biesecker, M.D.
  • Heidi Rehm, Ph.D., F.A.C.M.G.
10 Estimating Impact: How can we predict the variants most likely to have an effect on biological function?
Estimating Impact Workgroup:
  • Greg Cooper, Ph.D.
  • Stylianos Antonarakis, M.D., Sc.D.
  • Shamil Sunyaev, Ph.D.
  • Daniel MacArthur, Ph.D.
11 Experimental Data: How can we investigate whether candidate causal variants have a biological effect on disease risk?
Video | Slides
Experimental Data Workgroup:
  • Wendy Winckler, Ph.D.
  • Len Pennacchio, Ph.D.
  • Jay Shendure, M.D., Ph.D.
  • John Stamatoyannopoulos, M.D., Ph.D.
12 Clinical Implications: How could these guidelines be used in context of diagnostic-decision-making?
Video | Slides
Clinical Implications Workgroup:
  • David Adams, M.D., Ph.D.
  • Euan Ashley, M.R.C.P., D.Phil
  • David Dimmock, M.D.
  • David Valle, M.D.
13 Integrated Approach: How can we sum across different classes of evidence to assess overall confidence in variant causality?
Video | Slides
Integrated Approach Workgroup:
  • Mark Daly, Ph.D.
  • Don Conrad, Ph.D.
  • Mark Gerstein, Ph.D.
  • Chris Gunter, Ph.D.
14 Outline of White Paper / Summary of Key Messages and Next Steps
Daniel MacArthur, Ph.D.
Massachusetts General Hospital

Teri Manolio, M.D., Ph.D.
National Human Genome Research Institute


Last updated: September 12, 2012