Genetic epidemiology 15/11/22

Question 1

What is epidemiology?

Answer 1

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

Question 2

What is epidemiology used for?

Answer 2

It can provide answers about different groups of people and how different lifestyle factors, access to health care, legislation, cultural, and genetics effect a particular group of people.

Question 3

What is genetic epidemiology?

Answer 3

*Prevalence and incidence of genetic disorders
* Identifying genetic causes of disease
* Gene environment interaction in genetic disorders
* Treatments for genetic disease: Pharmacogenetics

Question 4

What is prevalence?

Answer 4

Prevalence is the number of cases of a disease or event present in a defined population at any
particular point in time.

Question 5

What is incidence?

Answer 5

Incidence is the number of new or newly recorded cases of the disease or events occurring within a
specified time period.

Question 6

What is prevalence increased by?

Answer 6

-Long duration of disease
-Prolongation if life (without cure)
-Increase in new cases
-In-migration of cases
-Out-immigration of healthy people
-Improved diagnostics

Question 7

What is prevalence decreased by?

Answer 7

-Shorter duration of disease
-High case-fatality rate
-Decrease in new cases
-In-migration of healthy people
-Out-immigration of cases
-improved cure rate of cases

Question 8

Can epidemiology facts be trusted globally?

Answer 8

No. Different countries have different testing strategies different access to health care and different ways of reporting statistics therefore global statistics can’t always be treated.

Question 9

What is a linkage study?

Answer 9

Genetic linkage analysis is a powerful tool to detect the chromosomal location of disease genes. It is based on the observation that genes that reside physically close on a chromosome remain linked during meiosis. We can use these to track segments of DNA through different generations and use this to find out where disease causing genetic variations are located and how the genetic variants are inherited, especially if they are disease causing.

Question 10

What is transmission disequalibrium?

Answer 10

It is a family-based association test for the presence of genetic linkage between a genetic marker and a trait. A specificity of the TDT is that it will detect genetic linkage only in the presence of genetic association. While genetic association can be caused by population structure, genetic linkage will not be affected, which makes the TDT robust to the presence of population structure.

Question 11

What is cross-sectional study?

Answer 11

Cross-sectional studies are quick to conduct as compared to longitudinal studies.
A cross-sectional study is conducted at a given point in time.
Cross-sectional study if repeated is conducted with different participants.
Cross-sectional studies cannot pin down cause-and-effect relationship.
Cross-sectional study is comparatively cheaper.

Question 12

What is a longitudinal study?

Answer 12

Longitudinal studies may vary from a few years to even decades.
A longitudinal study requires a researcher to revisit participants of the study at proper intervals.
Longitudinal study is conducted with the same participants over the years.
Longitudinal study can justify cause-and-effect relationship.
Since the study goes on for years longitudinal study tends to get expensive.

Question 13

What is a cohort study?

Answer 13

It is a type of longitudinal study where they follow people through life to look at health factors and genetics.

Question 14

What kind of study do you need when researching a rare disease?

Answer 14

Need a large population size to reflect real life.

Question 15

What are random errors?

Answer 15

This is when random error happens that introduces noise, but it is completely random, and this effects the reliability. It is a chance difference between the observed and true values of something (e.g., a researcher misreading a weighing scale records an incorrect measurement).

Question 16

What are systemic errors?

Answer 16

It is a consistent or proportional difference between the observed and true values of something (e.g., a miscalibrated scale consistently registers weights as higher than they actually are).

Question 17

What is internal validity?

Answer 17

Extent to which the results of the study reflect the true situation in the study sample.

Question 18

What is external validity?

Answer 18

Are the results of the study applicable to other populations than the study population.

Question 19

What do researchers want studies to have?

Answer 19

Reliability and validity as it makes it precise and accurate, however, validity is more important.

Question 20

What is confounding?

Answer 20

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 21

What is admixture?

Answer 21

Genetic admixture occurs when previously diverged or isolated genetic lineages mix. Admixture results in the introduction of new genetic lineages into a population.

Question 22

What is linkage disequilibrium?

Answer 22

The non-random association of alleles at different loci in a given population. Things that are physically attached will be inherited together. Linkage disequilibrium (LD) is a population-based parameter that describes the degree to which an allele of one genetic variant is inherited or correlated with an allele of a nearby genetic variant within a given population (Bush and Moore, 2012).

Question 23

What is Mendel’s law of independent assortment?

Answer 23

Mendel’s law of independent assortment states that the alleles of two (or more) different genes get sorted into gametes independently of one another. In other words, the allele a gamete receives for one gene does not influence the allele received for another gene.

Question 24

What is a haplotype?

Answer 24

A combination of closely linked DNA sequences variants on one chromosome that are often
inherited together.

Question 25

What is imputation?

Answer 25

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

Question 26

What is D prime (D’)?

Answer 26

It is an indicator of allelic segregation for two genetic variants. D’ values range from 0 to 1 with higher values indicating tight linkage of alleles. A D’ value of 0 indicates no linkage of alleles. A D’ value of 1 indicates at least one expected haplotype combination is not observed.

Question 27

What is R squared (R^2)?

Answer 27

It is a measure of correlation of alleles for two genetic variants. R2 values range from 0 to 1 with higher values indicating a higher degree of correlation. An R2 value of 0 indicates alleles are independent, whereas an R2 value of 1 indicates an allele of one variant perfectly predicts an allele of another variant. R2 is sensitive to allele frequency.

Question 28

What is SNP array?

Answer 28

SNP array is a type of DNA microarray which is used to detect polymorphisms within a population. A single nucleotide polymorphism (SNP), a variation at a single site in DNA, is the most frequent type of variation in the genome. Around 335 million SNPs have been identified in the human genome, 15 million of which are present at frequencies of 1% or higher across different populations worldwide.

Question 29

What is positive association?

Answer 29

Two variables have a positive association when the values of one variable tend to increase as the values of the other variable increase.

Question 30

What is no association

Answer 30

A value of zero indicates that there is no relationship between the two variables.

Question 31

Why is it important to study the cause of diseases in different populations?

Answer 31

Different genetic causes can cause disease in different populations?

Question 32

What is population stratification?

Answer 32

This is the presence of multiple subpopulations (e.g., individuals with different ethnic background) in a study. Population stratification can lead to false positive associations and/or mask true associations because of differences between subpopulations including:
* Allele frequencies
* Linkage disequilibrium patterns
* Variation in causal variant or variants
* Environmental factor

Question 33

What is information bias?

Answer 33

Bias in an estimate arising from measurement errors.

Question 34

What are examples of information bias?

Answer 34

Misclassification - how do you define your target population?
Data collection - will the question be understood? Will it be answered truthfully? Are your questions unbiased? Are the questions prone to cultural bias?

For example, three people with phenotypes of Marfan syndrome, only two of them actually have Marfan and the other has homocystinuria.

Question 35

What is selection bias?

Answer 35

Distortions that result from procedures used to select subjects and from factors that influence participation in the study.” Porta M. A dictionary of epidemiology. Oxford, 2008.

Question 36

What can selection bias lead to?

Answer 36

A non-representative sample.

Question 37

How to adjust for confounding?

Answer 37

Analysis stage - analytic methods of adjustment attempt to determine how the groups would have compared if they had been comparable with respect to one or more confounding factors. As such, they provide an estimate of effect (association) that is closer to the truth. These are:
- Stratification
- Multivariate Analysis
Randomisation of control trail
Restriction