Summary and Recommendations

1
Summaryand Recommendations

• Multi-IC NIH Symposium
• On Population Genomics
• June 6, 2006

2
Objectives of Symposium

• To identify common, critical issues that have
  been encountered in applying genomic technologies
  to population studies at NIH and creative
  approaches to solving them
• To develop approaches for prioritizing and
  conducting population studies using genomic
  technologies for use by individual ICs as desired
• To identify new tools for genomics,
  categorization of phenotypes, and database
  standardization required for genome-wide
  association and sequence-based studies.

3
Proposed Symposium Outcome

• Recommendations to the various ICs for issues to
  consider in soliciting, funding, and implementing
  these studies
• Shared experience and guidelines, not
  proscriptions
• Capable of updating and evolution
• Recommendations for new genomic tools needed for
  population studies and approaches for
  facilitating their use

4
Other Groups Are Tackling Some of the Priority
Issues Identified Here

• Pharmacogenetics Research Network (PGRN)
• GAIN (www.fnih.org)
• Trans-NIH Group on GWAS policies (Nabel, Shurin,
  and others)
• Genes and Environment Initiative (GEI)
• Genetics Subcommittee and its six Working Groups
• Exposure Biology Subcommittee
• Trans-NIH Bioethics Committee (T-NBC)
• NCBI Database Efforts
• Individual IC efforts

5
Proposed Symposium Outcome

• Recommendations to the various ICs for issues to
  consider in soliciting, funding, and implementing
  these studies
• Shared experience and guidelines, not
  proscriptions
• Capable of updating and evolution
• Recommendations for new genomic tools needed for
  population studies and approaches for
  facilitating their use

6
Shared GuidelinesConsent and IP Issues

• Standard trans-NIH policies for consent, data
  release, IP, publication (Nabel/Shurin GWAS panel
  already has the charge to pursue this across NIH)
• Elements of model consent for ongoing studies, or
  for reconsenting purposes
• Research studies to assess public concerns about
  research use, and whether the consent process
  works
• IRB education about acceptability of broad
  consent, data sharing, etc.
• Use of central IRBs?
• Database of successful consortium agreements

7
Shared GuidelinesData Formats

• Develop standard data formats across studies?
• Short term
• Long term
• Central standardized database for genotypes and
  phenotypes
• Need to strengthen the caBIGNCBI connection
• How to pay for this?
• Require PIs to provide a template for phenotype
  data at the time of application?
• Make data management and data usability part of
  the review criteria?

8
Collaborative Studies

• Compendium of currently funded case-control and
  cohort studies www.clinicaltrials.gov?
• Adding phenotypic and exposure measures to
  existing studies
• Initiating a large scale population based
  prospective cohort study in the U.S.?

9
Proposed Symposium Outcome

• Recommendations to the various ICs for issues to
  consider in soliciting, funding, and implementing
  these studies
• Shared experience and guidelines, not
  proscriptions
• Capable of updating and evolution
• Recommendations for new genomic tools needed for
  population studies and approaches for
  facilitating their use

10
What Tools Do We Need?(genotyping)

• More extensive data base of uncommon SNPs
  (MAFlt5)
• Comprehensive GWA panels for different
  populations
• Flexible and cost-effective technologies for
  small to large studies (1 to 106 SNPs)
• Better methods to score structural variations
• Standards for quality of genotyping

11
What Tools Do We Need?(phenotyping)

• Better methods for phenotyping
• Rigorous
• Standardized
• Inexpensive
• Non-invasive
• Limited time requirement for participants
• Phenotypes on controls need to be excellent also
• More accurate measurements of environmental
  exposure

12
What Tools Do We Need?(analysis)

• Define validation and replication
• Standards for declaring an association valid
• Standards for replications in other populations
• Improved analytical methods
• Weighting of SNPs according to prior likelihood
• Gene-environment interactions
• Gene-gene interactions
• Deposit of data from lots of control samples to
  increase power of ALL studies

13
What Tools Do We Need?(sequencing)

• Continued improvements in sequencing technology,
  moving toward the 1000 genome
• Effective methods for targeted resequencing of
  regions that show evidence of association
• Automated data analysis tools to identify
  heterozygotes in DNA sequence traces
• Rigorous algorithms to decide how to do followup
  sequencing which DNA samples, over what
  interval, and what fraction of the interval?

14
Thanks to All!

• Especially panel chairs and members
• And the organizing committee
• And Eva, Stephen, and Susan
• All of you have proven that 6/6/06 is not
  diabolical after all!
• Theres more work to do as usual but in the
  cause of really interesting science