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Human Genome Epidemiology HuGE Outline

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Human Genome Epidemiology HuGE Outline

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    1. Human Genome Epidemiology (HuGE) Outline Objectives Historical Perspectives Epidemiology in Post Genome Project era Definitions and Scope HuGE Continuum Gene discovery Gene Characterization Assessing genetic tests

    2. “Breakthrough of the Year” “For 2000, one word sums it up-GENOMES” Science (December 2000)

    3. Human Genes and Disease 2002 Human Genes 35,000 OMIM Entries 14,000 GeneTests Entries 1000

    4. Course Objectives Overall Introduce participants to an epidemiologic approach to the range of data from gene discovery to assessing genetic tests Specific Key genetic and epidemiologic concepts Identifying types of studies and measures Show examples from the literature

    5. Human Genome Epidemiology: Historical Perspectives 1 1865 -Mendel 1865 -Galton 1902 -Inborn errors 1908- Hardy-Weinberg 1918-Fisher- 1954 -Neel & Schull 1965 Chronic Disease Plant Experiments Family Resemblance Alkaptonuria Population Genetics Polygenes “Epidemiological Genetics” Conference

    6. Human Genome Epidemiology: Historical Perspectives 2 1973 – Pharmacogenetics 1978 -Ecogenetics 1978 -N.E. Morton 1984 -New Journal 1990 – HGP 1991- Society 1998- HuGE Net Drug Response GE Interaction First book Genetic Epi NIH/DOE IGES Genetics & Public Health Conferences

    7. I ”Identification of a Novel Common Genetic Risk Factor for Lumbar Disk Disease” P. Paassilta JAMA April 11, 2001   “A team of researchers has identified a genetic risk factor for a debilitating lower back disorder, opening the door to new ways to prevent, diagnose and treat a disease that affects millions of people worldwide” Reuters health (4/2001) Case-control study in Finland 171 LDD (MRI dx) 321 “controls” Collagen IX Trp3 allele 12.2% in cases vs. 4.7% in controls (3-fold risk)

    8. “Genetic Defect Doubles Colon Cancer Risk” Laken SJ et al. Nat Genetics 1997;17:79-83. “Researchers have found a new genetic defect present in one of every 17 American Jews that doubles a person's colon cancer risk”. “The good news is that scientists have developed a blood test, available for $200, that can detect this genetic defect. The test is advisable for everyone in the Ashkhenazi population, whether they have a family history of colon cancer or not.” http://www.preventcancer.org/ coloncancer.html

    9. Gene-Based Medicine in 2010? Collins FC, New Engl J Med 1999;341:28-37. Condition Genes RR Lifetime Prostate Ca HPC1, 2, 3 0.4 7% Alzheimer’s APOE,FAD3,XAD 0.3 10% Heart disease APOB,CETP 2.5 70% Colon Cancer FCC4,APC 4.0 23% Lung Cancer NAT2 6.0 40%

    10. Epidemiology (#@??!!) What is Epidemiology? “The study of the distribution and determinants of health-related states or events in populations, and the application of this study to control health problems” JM Last (1995) “Epidemiologists drive us crazy” S Mirsky, ScientificAmerican (2000)

    11. Epidemiology in the 21st Century:Population Impact of Human Genome Variation “Calculation, Communication, and Intervention” “The sequencing of the human genome offers the greatest opportunity for epidemiology since John Snow discovered the Broad Street pump” Shpilberg et al. J Clin Epidemiol (1997)

    12. Dissecting Human Disease in the PostGenome Era: The Importance of Epidemiology “Although experimental species are of great value for the initial identification and functional analysis of complex disease genes, final evidence for the involvement of these genes in human diseases must come from extensive epidemiological studies, preferably in different populations” Peltonen and McKusick, Science 2002;291:1224

    13. Emerging “Genomic” Methods in Epidemiology Susceptibility Exposure Outcomes DNA Polymorphisms RNA Studies (Toxicogenomics) Disease characterization (Proteomics)

    14. Limits of Individual Risk Prediction GA Colditz, AJPH 2001;91:357-359. “The complex pathophysiology suggest that prediction of disease at the individual level is meaningless in the short term and probably will never be applicable for widespread population use” “It is time to implement existing prevention strategies. It is also time to stop chasing after new risk factors”

    15. What is Genetic Epidemiology? The study of the role of genetic factors and their interaction with environmental factors in the occurrence of disease in human populations Khoury et al. Fundamentals of Genetic Epidemiology (1993)

    16. Human Genome Epidemiology (AKA Genetic Epidemiology with a Capital “E”) Applications of epidemiologic methods and approaches in evaluating the impact of human genome variation on health and disease in various populations HuGE involves a continuum from discovery to applications

    17. Human Genome Epidemiology: From Gene Discovery to Public Health Action Gene Discovery (classical genetic epidemiology) Family Studies Association Studies Gene Characterization (molecular epidemiology) Assessing Genetic Tests (applied epidemiology)

    21. Importance of the Epidemiologic Approach to Genetic Information Prevalence Associations Interactions Most current data based on selected unrepresentative populations Need for unbiased data on relative, absolute & attributable risks Enhances biologic plausibility and targeting interventions

    23. Epidemiologic Approach to Genetic Tests Analytic Validity Clinical Validity Clinical Utility How good is the test in measuring genotype? How good is the test in predicting clinical outcome? How good is the test and ensuing intervention in improving health and preventing disease?

    26. Human Genome Epidemiologic Data From Gene Discovery to Medical and Public Health Action Gene Discovery Gene location, function, variants Gene Characterization Prevalence, associations, interactions Assessing Genetic Tests Analytic validity Clinical validity and utility ELSI data Population impact

    27. Multidisciplinary Nature of Human Genome Epidemiology Genetics Clinical Medicine Laboratory Sciences Behavioral and Social Sciences Statistics

    28. Who Needs HuGE information? Policy makers Researchers Health care providers Consumers

    29. “The Genome is Mapped: Now What?” (M.D. Lemonick, Time Magazine 7/3/2000 p24) Gene Sequencing Gene Discovery Gene Characterization Clinical Utility Public Health Utility

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