Module 12 Flashcards
Molecular and Genetic Epidemiology
Used for figuring out how genes interact with environment to influence disease risk and outcome
Genetic epidemiology (definition)
Seeks to unravel the role of genetic factors and their interactions with environmental factors in the etiology of diseases, using family and population study approaches
Genetic epidemiology answers:
- Does a disease cluster in families?
- If so, is that clustering likely a result of shared non- genetic risk factors?
- If the clustering is not accounted for by shared lifestyle or common environment, is the pattern of disease consistent with inherited effects?
- If so, where is the putative gene?
Epidemiological assessment of clustering
- Case-control study
- Comparison of the frequency of a positive family history
- Expectation under genetic influence
Twin studies (natural experiment)
Greater concordance (for dichotomous traits) or correlation (for continuous traits) for MZ than DZ twins is evidence of a genetic influence
- Monozygotic (MZ) twins are genetically identical
- Dizygotic (DZ) twins share, on average, the same proportion of genes as siblings
Linkage analysis
Tracks region of DNA that is transmitted from parents to offspring in the same manner as the disease/outcome of interest
- works well for diseases that follow simple rules of inheritance (e.g., autosomal dominant or recessive).
- Linkage does not mean causality
Segregation analysis
Tests whether the observed pattern of disease in families is compatible with Mendelian model of genetic inheritance
Performed by statistically testing competing models
Complex diseases
Ones for which the genetic influence may be modest and environmental factors contribute to disease risk.
– Examples: Cancers, heart disease, AD
*Segregation analysis is not typically done for “complex diseases
Dementia
Collection of clinical symptoms of intellectual impairment (can be reversible, treatable)
Causes: AD, stroke, depression, trauma, medication
Alzheimer’s disease
- Progressive, neurodegenerative disease of the brain
- Impairment of cognitive and memory functions
- Changes in mood, personality, and behavior
- Risk factors: Age, Family history, Genetics
Management implications of AD
– Number of dementia cases expected to increase dramatically as population ages.
– Increased demand on healthcare system
Molecular epidemiology
Use of epidemiologic methods and techniques of molecular biology
Molecular v. Genetic Epidemiology
- Overlap between molecular epidemiology and genetic epidemiology when genes are involved in disease/exposure association
- Molecular epidemiology does not involve studies of biologically-related individuals
- Molecular epidemiology evaluates association of variation in known genes with disease risk
- Genetic epidemiology identified unknown genes that influence disease risk
Biomarkers
- A cellular or molecular indicator of exposure or health effect
- Identified from biologic specimens (blood, sputum, urine, tissue, etc)
Benefits of molecular epidemiology
– Greater precision in estimating exposure- disease associations
– Provide early warnings for disease by flagging preclinical effects of exposure
– Identifies level of exposure based on relevant biomarkers for particular diseases/health conditions
