Introduction to Molecular Epidemiology

Jan Dorman, PhDUniversity of PittsburghSchool of Nursingjsd@pitt.edu

Revolution in Molecular Biology has Impacted: Science Medicine

Society Epidemiology

Molecular EpidemiologyChallenge 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

Exposure Disease

Black Box

Effects ofenvironmental 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

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 ModifiersMutation + 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 MarkersMutation + 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 forMolecular 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 EpidemiologyChallenge for the 21st Century