Population genetics

Question 1

What does association testing test between

Answer 1

exposure and disease

alleles/genotypes on SNP and trait of interest

Question 2

How are alleles and genotypes coded in association testing

Answer 2

alleles- 0, 1

genotypes-0, 1, 2

Question 3

What is GWAS, what is its prequisite and how is it performed

Answer 3

What: search for causal variants associated with pheotype everywhere in genome. susceptibility locus discovery
Prequisite: trait must be known to be heritable
How to: one SNP at a time, on one outcome of interest

Question 4

How is GWAS result ilustrated, what do lines and Y axis mean

Answer 4

Manhattan plot
line shows how much correlation
Y axis==P values that are log transformed into base 10

Question 5

what can genetics be used for and what is the future aim

Answer 5

Currently: predict height, BP, cholersterol, IQ, alchool consumption, extraversion
Future: Predict what diseases people may get->personalised medicine

Question 6

How can we overcome the difficulty of individual level disease prediction

Answer 6

aggregating predictions acrosss samples allow powerful group level inference and many different applications

Question 7

Why predict in groups of people

Answer 7

many questions can be answered by comparing predictions in groups of people
WIth larger GWAS sample, predictions at individual level will be accurate soon

Question 8

How do we do prediction from genetics

Answer 8

for polygenic complex traits, include more variants->so long as they are enriched for real signal. Perhaps more accurate predictions by including more SNPs

Question 9

What are polygenic risk scores

Answer 9

score that predicts individual’s risk of dissease based on combo of their genotype and effect size estimates from GWAS result

Question 10

How can polygenic risk scores be useful for research

Answer 10

can assess shared genetic aetiology among phenotype, act as biomarker for disease, infer whether biological factor is causally associated with disorder and screen subjects for clinical trials

Question 11

What is the method of calculating PRS

Answer 11

Predicts individual’s trait value from genetic profile
sum of risk alleles from genome wide SNPs weighted by their GWAS derived effect size estimates
Only SNPs exceeding P value threshold in discovery of GWAS contribute to score.
PRS calculated for several Pt in individuals of target data set.
Regressionn is then performed to ttest for association between PRS and trait in target sample