Introduction to Molecular Epidemiology Jan Dorman, PhD University of Pittsburgh School of Nursing

Revolution in Molecular Biology has Impacted: Science Medicine Society Epidemiology Molecular Epidemiology Challenge for the 21st Century

Molecular Epidemiology Will facilitate the ability of scientists to conduct etiologic research Will increase our knowledge about the determinants of disease Will contribute to the development of approaches for disease prevention Will improve public health

Genetic Epidemiology A science that deals with etiology, distribution and control of disease in families and with inherited causes of diseases in populations N Morton

Genetic Epidemiology Is based on population genetics Utilizes statistical techniques to evaluate the genetic aspects of chronic diseases Little or no emphasis on environmental risk factors

Genetic Epidemiology Includes the fundamental interaction between genetic variation with the environment in the occurrence of disease M Khoury

Many studies are still focused on the identification of disease susceptibility genes –New SNP and haplotype maps –New approaches to linkage analysis - High through-put molecular techniques Genetic Epidemiology

Results are not generalizable to the population at large Requires Molecular Epidemiology Genetic Epidemiology

Origins of Molecular Epidemiology CancerInfectious Diseases Descriptive and Analytical Epidemiology

Molecular Cancer Epidemiology An approach in which advanced laboratory methods are used with analytical epidemiology to identify, at the biochemical or molecular level, specific exogenous agents and / or host factors that play a role in human cancer causation F. Perera

Traditional Cancer Epidemiology ExposureDisease Black Box Effects of environmental exposures

Molecular Cancer Epidemiology Use of biological markers to examine parts of a continuum between an initiating event and the development of disease ExposureDisease Inside the Black Box

Molecular Epidemiology Black Box Exposure Genetic Susceptibility Effect Disease

Molecular Epidemiology A science that deals with the contribution of genetic and environ- mental risk factors identified at the molecular and biochemical level, to the etiology, distribution and control of disease in families and populations J. Dorman

Molecular Epidemiology Dissolved boundaries between traditional epidemiology and: -Human genetics -Molecular genetics –Molecular biology Requires decisions about collecting, processing and storing biological specimens

Molecular Epidemiology Requires consideration of standardization, analytical validity and clinical validity of molecular tests Utilizes family study designs, as well as case-control and cohort studies

Is not just a term that describes adding new techniques to epidemiology. Rather, it represents an opportunity to use new resolving power to develop theories of disease causation that acknowledge complex interactions in the health process. P Schulte Molecular Epidemiology

Molecular Epidemiology is a Critical Link Human Genome Project Molecular Epidemiology Medicine and Public Health

Human Genome Project and Epidemiology Map and sequence ~ 30,000 genes Development of biotechnology Ethical, legal and social issues Map and sequence non-human genomes Markers of disease and susceptibility Technology for population studies Screening and prevention Models for disease, identify susceptibility genes

Objectives of Molecular Epidemiology Conduct descriptive and analytical studies to evaluate gene / environment interactions in disease etiology Provide risk factor-specific morbidity rates for purposes of education and intervention

Personalized estimates of risk may empower susceptible individuals to intervene on: –- Diet, lifestyle –- Environmental exposures Targeted approaches may be more effective in preventing disease Molecular Epidemiology and Disease Prevention

Descriptive Epidemiology Examines the distribution of disease - By person, place and time - Consequences to population Rates are expressed as incidence and prevalence (i.e., morbidity rates)

Assesses effects and / or outcomes early in the disease process Reduces heterogeneity in disease classification Examines the distribution of markers of susceptibility or exposure Descriptive Molecular Epidemiology

Analytical Epidemiology Evaluates associations with potential risk factors –Host characteristics –Environmental exposures Associations are expressed as relative risks or odds ratios

Utilizes biological markers to replace surrogate measures that have been typically employed for traditional epidemiologic studies –Genetic susceptibility –Environmental exposures or effects Analytical Molecular Epidemiology

Environmental Risk Factors Place of residence Lifestyle / occupational indicators Biological markers of exposure - Alterations to the host genome - Antibodies - Infectious agents More precise measure of exposure

Genetic Susceptibility Age, race, sex, ethnic group Positive family history of the disease Genetic markers / susceptibility genes - Protein polymorphisms - DNA polymorphisms More precise measure of susceptibility

Evaluating Genes as Effect Modifiers Mutation + Exposure = High Risk Mutation + No Exposure = Low Risk No Mutation + Exposure = Low Risk No Mutation + No Exposure = Low Risk Study Disease Etiology

Evaluating Genes as Susceptibility Markers Mutation + Exposure = High Risk Mutation + No Exposure = Moderate Risk No Mutation + Exposure = Moderate Risk No Mutation + No Exposure = Low Risk Intervene on Susceptibles

Risk Factor-Specific Morbidity Rates Descriptive Analytical Absolute risk Relative risk Population attributable risk

Molecular Epidemiology Requires Collaboration among: - Epidemiologists - Human geneticists - Environmental health scientists - Health professionals - Biostatisticians - Basic scientists

Challenges for Molecular Epidemiology Develop and sustain collaboration among individuals with different - Backgrounds - Training - Experience - Goals - Language

Challenges for Molecular Epidemiology Training Human genetics, molecular biology and environmental health for epidemiologists and health professionals Epidemiology and public health for human geneticists and basic scientists

Challenges for Molecular Epidemiology Translations of the results of molecular epidemiology studies Foster links with: - Members of the community - Policy makers - Educators - General public

Revolution in Molecular Biology has Impacted: Science Medicine Society Epidemiology Molecular Epidemiology Challenge for the 21st Century