Public Health Genomics: Using Genomic Knowledge for Population Health

1. Public Health Genomics: Using Genomic Knowledge for Population Health Cynthia A. Moore, MD, Ph.D. National Office of Public Health Genomics Centers for Disease Control and Prevention The findings and conclusions in this presentation have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy.

2. Almost All Diseases are Caused by Gene-Environment Interaction Gene + Environment Environmental Genetic e.g., Sickle Cell Anemia e.g., Injury Heart Disease Asthma Diabetes Preterm Birth

3. Genetics vs. Genomics • Genetics: The study of single genes and their effects • Genomics: The study not just of single genes but of the functions and interactions of all the genes in the genome Guttmacher and Collins. New Engl J Med 2002;347:1512-20. • Genetics  Genomics: A continuum from genetic disease to genetic information Khoury. Genet Med 2003;5:261-8.

4. Genetics Genomics in Health Practice  • Genetic Disease • Mendelian Disorders • Disease Burden: 5% • Mutations/One Gene • High Disease Risk • Environment +/- • “Genetic Services” • Genetic Information • All Diseases • Disease Burden: 95% • Variants/Multiple Genes • Low Disease Risk • Environment ++ • General Practice

5. Outline • Global Emergence of “Public Health Genomics” • The role of a “population perspective” • Expansion of Population-based Research • What do genomic applications mean for real populations? • Crucial role of Knowledge Synthesis and Integration • How do we find needles in a haystack? • Need for Public Health Assessment of Genome-based Tests and Technologies • Evidence-based health care

6. What is “Public Health Genomics”?(Bellagio Report, 2006) • “A multidisciplinary field concerned with the effective and responsible translation of genome-based knowledge and technologies to improve population health”

7. The Public Health Genomics Enterprise Genome-based Science and Technology Improvement in Population Health

8. The Public Health Genomics Enterprise Communication and Stakeholder Engagement Population Sciences Informing Public Policy Knowledge Integration Within And Across Disciplines Genome-based Science and Technology Improvement in Population Health Humanities and Social Sciences Developing and Evaluating Health Services Educationand Training

9. Importance of the Epidemiologic Approach to Genetic InformationBeyond Gene Discovery Prevalence Associations Interactions Data from representative populations needed for research & programs Need for population specific data on relative, absolute & attributable risks Data needed to enhance biologic plausibility and to develop interventions

10. “Systematic application of epidemiologic methods and approaches to assess the impact of human genetic variation on health and disease” Khoury, Little and Burke, HuGE 2004 • Genotype prevalence • Gene - disease association • Gene - gene interactions • Gene - environment interactions • Assessment of genetic tests HuGE problem: 25,000 genes, their combinations and interactions with risk factors

11. Population Health Research in the “Genomics” Era

12. Emergence of Global Biobanks and Cohort Studies

13. The Public Health Genomics Enterprise Communication and Stakeholder Engagement Population Sciences Informing Public Policy Knowledge Integration Within And Across Disciplines Genome-based Science and Technology Improvement in Population Health Humanities and Social Sciences Developing and Evaluating Health Services Educationand Training

14. Collaboration to Assess Impact

15. Human Genome Epidemiology Network (HuGENet) Global collaboration of individuals and organizations to assess population health impact of human genomic variation and how it can be used to improve health and prevent disease in populations

16. Genomic Tests: A Public Health Issue Potential to affect many people (i.e., pharmacogenomics) Potential for enhancing and targeting prevention efforts Implementation and access Provider and public education Monitoring impact on population health

17. “Gene Increases Diabetes Risk, Scientists Find” (New York Times, January 16, 2006) “Scientists have discovered a variant gene that leads to a sizeable extra risk of Type 2 Diabetes and is carried by more than a third of Americans…An immediate practical consequence of the discovery would be to develop a diagnostic test to identify people who carry the variant gene. If people knew of their extra risk, they would have an incentive to stay thin and exercise” Grant et al. Nat Genet Jan 2006

18. For each intended use Four components of evaluation Analytic Validity Clinical Validity Clinical Utility ELSI Define test, disorder, and setting Analytic framework – 40+ targeted questions Knowledge Integration Across Disciplines: Evaluation of Genetic Tests http://www.cdc.gov/genomics/activities/fbr.htm

19. EGAPP Evaluation of Genomic Applications in Practice and Prevention CDC-funded pilot project Non-regulatory Independent, non-federal, multidisciplinary Working Group Minimize conflicts of interest Integrates existing processes for evaluation and appraisal Evidence-based, transparent, and publicly accountable

20. Evaluation of Genomic Applications in Practice and Prevention (EGAPP)

21. “Genomic profiling to promote a healthy lifestyle: not ready for prime time”Haga S et al. Nat Genet 2003

22. The Public Health Genomics Enterprise Genome-based Science and Technology Improvement in Population Health Closing the Gap Between Gene Discovery and Population Health

23. Public Health Genomics at CDC www.cdc.gov/genomics