Genetic Epidemiology

Question 1

advantages of genome wide association studies (GWAS)?

Answer 1

useful for studying diseases where the underlying biological mechanisms are unknown

can lead to better understanding of a disease

Question 2

disadvantages of genomic-wide association studies?

Answer 2

• All significant associations have to be independently replicated to be considered robust.
• A robust association between a genetic marker and a disease does not mean it is causative.
• small effect size of some eugenic loci means large sample sizes are needed to have sufficient power.

Question 3

what are genome-wide association studies (GWAS)?

Answer 3

a special type of association study in which genetic markers are analysed covering the whole genome.

currently the most widely used method to discover genetic associations with a disease.

Question 4

how is the relative recurrence risk ratio calculated?

Answer 4

prevalence of disease in relatives of affected person / prevalence of disease in general population

Question 5

what does it mean if twins are discordant?

Answer 5

one has the disease and one doesn’t

Question 6

what does it mean if twins are concordant?

Answer 6

both have the disease or both do not have the disease

Question 7

what do adoption studies do?

Answer 7

compares disease concordance with biological parents to concordance with adoptive parents

Question 8

what does segregation analysis do?

Answer 8

• analyses the mode of inheritance of a disease and how many genes are involved.
• involves studying extended families to see if inheritance of the disease follows a particular pattern.

Question 9

define linkage

Answer 9

the tendency for 2 or more genetic loci to be inherited together due to close physical proximity (they are on the same chromosomes)

Question 10

what is a haplotype?

Answer 10

when recombination events create new combinations of alleles.

Question 11

what is the recombination fraction?

Answer 11

the probability of 2 genetic markers segregating independently.

Question 12

what are linkage studies?

Answer 12

a method for determining the region of the genome that contains a disease susceptibility locus.

uses genetic markers and assesses how often these markers co-segregate with the disease.

Question 13

what are parametric linkage studies?

Answer 13

makes certain assumptions about the disease, the main one being the mode of inheritance.

Question 14

what is an LOD score?

Answer 14

a statistical measure of the likelihood of genetic linkage between 2 loci.

Question 15

what are some limitations of linkage studies?

Answer 15

They require a large number of families or families with large pedigrees:

• Loss of power
• Large number of studies are not replicated.

The disease susceptibility regional’s can be very large:
- Can make it hard to locate the causative mutation
- Provides the input for candidate gene studies

Question 16

what do association studies do?

Answer 16

look for genetic markers that occur more or less often in disease than the general population.

Question 17

which studies are effective at identifying genetic risk factors?

Answer 17

association studies

Question 18

how are family based studies analysed?

Answer 18

using the transmission disequilibrium test (TDT)

Question 19

what is linkage disequilibrium?

Answer 19

the non-random correlation of alleles at 2 different loci.