Introduction to Molecular

Epidemiology

Jan Dorman, PhD

University of Pittsburgh
School of Nursing
jsd@pitt.edu
Revolution in Molecular
Biology has Impacted:
 Science  Society
 Medicine  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 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
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  Markers of disease
~ 30,000 genes and susceptibility
 Technology for
 Development of
population studies
biotechnology
 Screening and
 Ethical, legal and prevention
social issues  Models for disease,
 Map and sequence identify susceptibility
non-human genomes 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 = 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  Society
 Medicine  Epidemiology

Molecular Epidemiology
Challenge for the 21st Century