Pgx Drug Discovery I

Question 1

Null Hypothesis

Answer 1

no association between any allele and drug resistance

Question 2

P > 0.1

Answer 2

no presumption against the null hypothesis (no significant association)

Question 3

0.05 < P < 0.1

Answer 3

low presumption against the null hypothesis (marginal association)

Question 4

P < 0.05

Answer 4

strong presumption against the null hypothesis (significant association)

Question 5

P < 0.01

Answer 5

very strong presumption against the null hypothesis (very significant association)

Question 6

Does the p value measure the strength of association of relationship?

Answer 6

NO
- affected by sample size or allele frequency

Question 7

Measure of the strength

Answer 7

Odds Ratio

Question 8

Odds Ratio

Answer 8

increased risk for a phenotype by carrying a specific genotype/allele compared to patients without carrying

Question 9

Odds Ratio Equation

Answer 9

odds of phenotype in an individual with genotype / odds of genotype in an individual without genotype

Question 10

OR = 1

Answer 10

no association

Question 11

OR > 1

Answer 11

potentially increases the risk

the higher the OR is, the higher risk the allele will confer to phenotype

Question 12

OR < 1

Answer 12

potentially decreases the risk

the smaller the OR is, the lower risk the allele will confer to phenotype

Question 13

95% Confidence Interval

Answer 13

• statistical probability for the odds ratio (standard of error of OR)

Question 14

95% CI > 1

Answer 14

significant risk effect

Question 15

95% CI includes 1

Answer 15

no statistical significance

Question 16

95% CI < 1

Answer 16

significant protective effect

Question 17

Correction for P Values

Answer 17

• due to a large number of tests for many SNP’s vs the single phenotype, there is a much higher probability to have many SNPs associated with the phenotype just by chance –> multiple testing
• the more SNPs tested, the higher probability for a false positive

Question 18

Solution for false positive

Answer 18

Bonferroni corretion:
- corrected P = 0.05 / N

IN GENERAL WE USE 5x10^-8 AS CORRECTED SIGNIFICANT GWAS P VALUE

Question 19

Experiments to Test Hypothesis

Answer 19

CONTROL IS THE KEY (positive & negative control)

Requirements:
1. Sham (negative control)
2. Standard of Care Drug (positive control)
3. Investigational Drug (experiment group)

LARGE SAMPLE SIZE IS ESSENTIAL

CLINICAL STUDY OFTEN USES MEDIAN BUT NOT MEAN

TEST ONE CONCEPT IN MULTIPLE BIOLOGICAL SYSTEMS (molecular, cellular, rodents, human iPSC) TO MAKE RESULTS MORE RELIABLE

Question 20

What type of distribution do most studies follow?

Answer 20

normal (guassian) distribution (bell curve)

Question 21

Why do we use the MEDIAN and not the mean?

Answer 21

faster

patient data may not be normally distributed (skewness)