Lecture 15 (association studies) Flashcards
what are association studies?
find genetic variance associated with a disease and then find causal genes to allow us to target the disease in terms of drugs
What do association studies have to do with QTL mapping?
association studies can be used to map QTL via linkage disequilibrium mapping.
How can we use association studies for complex traits?
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
what do we consider a rare/common allele?
- 001-0.005 rare
- 005-0.05 (low freq)
- 5-1 (common)
whatcan’t association studies find?
rare alleles with small effect that occur at small freq
what can association studies find?
common variants with large effects are getting out of the pop so studies look at middle panel COMMON VARIANTS WITH SMALL EFFECTS
what do we mean by a common variant with a large effect?
when it has such a bad effect that they’re getting out of the population due to selection
what does MAF mean?
minor allele frequency refers to 1-5% in the pop
how does hap map work?
it uses linkage disequilibrium to look at SNPs
explain linkage equilibrium
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
explain Linkage disequilibrium
occurs when allele freq does not match haplotype freq because A is only associated with B and a is only associated with b
how can we calculate the maximum linkage disequilibrium?
D= PAB x Pab - PAb x PaB
what’s the correlation coefficient for? how is it calculated?
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
what can stop linkage disequilirbrium?
recombination.
how do we want a marker to be located?
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
characteristics of HapMap project
- 10 million SNPs
- 11 popilation and 1184 indv
what are LD maps?
plot of HapMap e.g there’s a marker and red shows significant association therefore LD
what is association mapping?
associate SNPs with a disease by looking at historical linkage and the recombination that has occurred since the mutation has first appeared
what are the two types of associations that we can find of a SNPs and a disease?
it can be directly found in the gene but it’s quite unlikely or it can be found as an indirect association
what are the two main approaches of association studies?
GWAS (look at whole genome to find variants
or candidate gene studies
what are the 6 requirements of association studies?
- score everyone in the same way
- do GWAS or candidate gene studies
- high sample size
- check pop structure
- statistical analysis
- fine mapping dor a more detailed analysis.
give an example of an association study using case controls
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
how’s the relative risk of a diasease calculated?
doing probabilities if RR is 1-1.5 low risk if >2 then large effect
what’s the welcome trust case control study?
it’s a study looking at 7 diseases and loads of imdv using GWA.
