Transcript 33891 - University of Pittsburgh

Introduction to Molecular
Epidemiology
Jan Dorman, PhD
University of Pittsburgh
School of Nursing
[email protected]
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
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
Genetic Epidemiology
Results are not generalizable to the
population at large
Requires Molecular Epidemiology
Origins of Molecular Epidemiology
Descriptive and Analytical Epidemiology
Infectious Diseases
Cancer
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
Exposure
Disease
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
Exposure
Disease
Inside the Black Box
Molecular Epidemiology
Genetic
Susceptibility
Exposure
Effect
Disease
Black Box
Molecular Epidemiology
A science that deals with the
contribution of genetic and environmental 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
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
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
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
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)
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
Analytical Epidemiology

Evaluates associations with potential
risk factors
– Host characteristics
– Environmental exposures

Associations are expressed as
relative risks or odds ratios
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
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
Mutation
+ No Exposure = Low Risk
No Mutation + Exposure
= High Risk
= Low Risk
No Mutation + No Exposure = Low Risk
Study Disease Etiology
Evaluating Genes as
Susceptibility Markers
Mutation
+ Exposure
Mutation
+ No Exposure = Moderate Risk
No Mutation + Exposure
= High Risk
= 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