Introduction to Molecular Epidemiology

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Introduction to Molecular Epidemiology

• Jan Dorman, PhD
• University of Pittsburgh
• School of Nursing
• jsd_at_pitt.edu

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Revolution in Molecular Biology has Impacted

• Science
• Medicine

• Society
• Epidemiology

Molecular Epidemiology Challenge for the 21st
Century
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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

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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

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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

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Genetic Epidemiology

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

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Genetic Epidemiology

• 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

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Genetic Epidemiology

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

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Origins of Molecular Epidemiology
Descriptive and Analytical Epidemiology
Cancer
Infectious Diseases
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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

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Traditional Cancer Epidemiology
Exposure
Disease
Black Box
Effects of environmental exposures
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Molecular Cancer Epidemiology

• Use of biological markers to examine parts of a
  continuum between an initiating event and the
  development of disease

Exposure
Disease
Inside the Black Box
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Molecular Epidemiology
Genetic Susceptibility
Exposure
Effect
Disease
Black Box
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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
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Molecular Epidemiology

• Dissolved boundaries between traditional
  epidemiology and
• Human genetics
• Molecular genetics
• Molecular biology
• Requires decisions about collecting, processing
  and storing biological specimens

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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

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Molecular Epidemiology

• 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

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Molecular Epidemiology is a Critical Link

• Human Genome Project
• Molecular Epidemiology
• Medicine and Public Health

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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

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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

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Molecular Epidemiology and Disease Prevention

• Personalized estimates of risk may empower
  susceptible individuals to intervene on
• - Diet, lifestyle
• - Environmental exposures
• Targeted approaches may be more effective in
  preventing disease

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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)

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Descriptive Molecular Epidemiology

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

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Analytical Epidemiology

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

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Analytical Molecular Epidemiology

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

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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

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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

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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

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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

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Risk Factor-Specific Morbidity Rates

Descriptive
Analytical
Relative risk
Absolute risk
Population attributable risk
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Molecular Epidemiology Requires

• Collaboration among
• - Epidemiologists
• - Human geneticists
• - Environmental health scientists
• - Health professionals
• - Biostatisticians
• - Basic scientists

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Challenges for Molecular Epidemiology

• Develop and sustain collaboration among
  individuals with different
• - Backgrounds
• - Training
• - Experience
• - Goals
• - Language

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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

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Challenges forMolecular Epidemiology

• Translations of the results of molecular
  epidemiology studies
• Foster links with
• - Members of the community
• - Policy makers
• - Educators
• - General public

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Revolution in Molecular Biology has Impacted

• Science
• Medicine

• Society
• Epidemiology

Molecular Epidemiology Challenge for the 21st
Century