Lecture 15 (association studies)

Question 1

what are association studies?

Answer 1

find genetic variance associated with a disease and then find causal genes to allow us to target the disease in terms of drugs

Question 2

What do association studies have to do with QTL mapping?

Answer 2

association studies can be used to map QTL via linkage disequilibrium mapping.

Question 3

How can we use association studies for complex traits?

Answer 3

many diseases that occur at a high frequency >1% in a pop, have several genes involved but if we sample enough individuals we can infer which are the genes that are involved. however there’s a counter hypothesis that estates that these diseases are due to rare alleles very difficult to find

Question 4

what do we consider a rare/common allele?

Answer 4

0. 001-0.005 rare
1. 005-0.05 (low freq)
2. 5-1 (common)

Question 5

whatcan’t association studies find?

Answer 5

rare alleles with small effect that occur at small freq

Question 6

what can association studies find?

Answer 6

common variants with large effects are getting out of the pop so studies look at middle panel COMMON VARIANTS WITH SMALL EFFECTS

Question 7

what do we mean by a common variant with a large effect?

Answer 7

when it has such a bad effect that they’re getting out of the population due to selection

Question 8

what does MAF mean?

Answer 8

minor allele frequency refers to 1-5% in the pop

Question 9

how does hap map work?

Answer 9

it uses linkage disequilibrium to look at SNPs

Question 10

explain linkage equilibrium

Answer 10

when you have two genes A and B and two alleles respectively and the allele freq will be the same then the haplotype freq match the allele freq this is LE

Question 11

explain Linkage disequilibrium

Answer 11

occurs when allele freq does not match haplotype freq because A is only associated with B and a is only associated with b

Question 12

how can we calculate the maximum linkage disequilibrium?

Answer 12

D= PAB x Pab - PAb x PaB

Question 13

what’s the correlation coefficient for? how is it calculated?

Answer 13

it’s used to compare bt different studies
r^2 = D/ PA PB Pb Pa
max LD is 1 and 0 is no LD thus LE

Question 14

what can stop linkage disequilirbrium?

Answer 14

recombination.

Question 15

how do we want a marker to be located?

Answer 15

the closer to the mutation as possible so the least change to be broken by recombination if there’s a marker close to the mutation –> strong LD

Question 16

characteristics of HapMap project

Answer 16

• 10 million SNPs

- 11 popilation and 1184 indv

Question 17

what are LD maps?

Answer 17

plot of HapMap e.g there’s a marker and red shows significant association therefore LD

Question 18

what is association mapping?

Answer 18

associate SNPs with a disease by looking at historical linkage and the recombination that has occurred since the mutation has first appeared

Question 19

what are the two types of associations that we can find of a SNPs and a disease?

Answer 19

it can be directly found in the gene but it’s quite unlikely or it can be found as an indirect association

Question 20

what are the two main approaches of association studies?

Answer 20

GWAS (look at whole genome to find variants

or candidate gene studies

Question 21

what are the 6 requirements of association studies?

Answer 21

1. score everyone in the same way
2. do GWAS or candidate gene studies
3. high sample size
4. check pop structure
5. statistical analysis
6. fine mapping dor a more detailed analysis.

Question 22

give an example of an association study using case controls

Answer 22

we have a pop with a disease and we take other imdv without disease, we suspect that having a G in certain position determines the disease however there’re people w/0 the disease that have it, we do a chi test and if p value is good then G is associated with a disease

Question 23

how’s the relative risk of a diasease calculated?

Answer 23

doing probabilities if RR is 1-1.5 low risk if >2 then large effect

Question 24

what’s the welcome trust case control study?

Answer 24

it’s a study looking at 7 diseases and loads of imdv using GWA.