Week 7: Population genetics and genetic epidemiology

Question 1

Epidemiology

Answer 1

Epidemiology is the study of the distribution and determinants of health related states or events (including disease) and the applications of this study to the control of diseases and other health problems

Question 2

Prevalence

Answer 2

The number of cases of a disease or event present in a defined population at any particular point in time.
Prevalence can be increased by:
- Long duration of disease
- Prolongation of life (without cure)
- Increase in new cases
- In-migration cases
- Out-migration of healthy people
- Improved diagnostics
Prevalence can be decreased by:
- Shorter duration of disease
- High case fatality rate
- Decrease in new cases
- In-migration of healthy people
- Out-migration of cases
- Improved care rate of cases

Question 3

Incidence

Answer 3

The number of newly recorded cases of the disease or events occurring within a specified time period

Question 4

Linkage studies

Answer 4

By knowing the position of specific genetic variants within each chromosome, we can use these to track segments of DNA through different generations

Question 5

Transmission disequilibrium

Answer 5

The transmission disequilibrium test (TDT) is a useful method to locate mutations linked to disease genes associated with complex diseases. TDT requires genotypes of affected individuals and their parents.

Question 6

Different inheritance patterns for Alzheimer’s (AD) (Early onset, dominantly inherited)

Answer 6

• Inherited, genetic mutations (eg. APP, Tau, Presenlins)
• 30 - 60 years of age at onset
• 1% of cases

Question 7

Different inheritance patterns for Alzheimer’s (AD) (Early onset, complex inherited)

Answer 7

• Genetic and environmental risk factors
• < 65 years of age at onset
• 4% of cases

Question 8

Different inheritance patterns for Alzheimer’s (AD) (Late onset, complex inheritance)

Answer 8

• Genetic and environmental risk factors
• > 65 years at age of onset
• 95% of cases

Question 9

Modifiable risk factors of dementia (increases risk)

Answer 9

Strong evidence - Traumatic brain injury
Moderate evidence - Mid-life obesity, mid-life hypertension, current smoker and diabetes
Unclear evidence - History of depression, sleep disturbances

Question 10

Modifiable risk factors of dementia (decreases risk)

Answer 10

Strong evidence - years of formal education
Moderate evidence - Physical activity
Lower evidence - Mediterranean diet, cognitive training
Unclear evidence - Moderate alcohol consumption

Question 11

Alzheimer’s genetics

Answer 11

• Different variants cause the same disorder
• Incomplete penetrance
• No single variant is necessary or sufficient to cause the disorder

Question 12

Studying populations

Answer 12

Case-control study
- A study that compares two groups of people: those with the disease or condition (case) and a very similar group of people that do not have the disease or condition (control)
Cohort study
- A type of longitudinal study - an approach that follows research participants over a period of time (often many years). Specifically, cohort studies recruit and follow participants who share a common characteristic

Question 13

Validity and reliability

Answer 13

Internal validity
- Extent to which the results of the study reflect the true situation in the study sample
External validity
- Are the results of the study applicable to other populations than the study population

Question 14

Confounding

Answer 14

Confounding is confusion, or mixing of effects; the effect of the exposure is mixed together with the effect of another variable, leading to bias

Question 15

Linkage disequilibrium

Answer 15

The non-random association of alleles at different loci in a given population. Things that are physically attached will be inherited together

Question 16

Mendel’s Law of Independent Assortment

Answer 16

Each pair of alleles segregates independently of other pairs of alleles

Question 17

Haplotype

Answer 17

A combination of closely linked DNA sequence variants on one chromosome that are inherited together

Question 18

Imputation

Answer 18

Refers to the statistical inference of unobserved genotypes. It is achieved by using known haplotypes in a population

Question 19

Population stratification

Answer 19

This is the presence of multiple subpopulations (eg. individuals with different ethnic backgrounds) in a study. Population stratification can lead to false positive associations and/or mask true associations because of differences between subpopulations including:
- Allele frequency
- Linkage disequilibrium patterns
- Variation in causal variant or variants
- Environmental factors

Question 20

Information bias

Answer 20

• How do you define your target population?
• Will the question be understood?
• Will it be answered truthfully?
• Are the questions unbiased?
• Are the questions prone to cultural bias?