9 - Drug Discovery 1

Question 1

How do you calculate the # of alleles from the number of genotypes in a case control study?

Answer 1

Question 2

What is the interpretation of P>0.1?

Answer 2

No presumption against null hypothesis (no significant association)

Question 3

What is the interpretation of 0.05<P<0.1?

Answer 3

Low presumption against null hypothesis (marginal association)

Question 4

What is the interpretation of P<0.05?

Answer 4

Strong presumption against null hypothesis (marginal association)

Question 5

What is the interpretation of P<0.01?

Answer 5

Very strong presumption against null hypothesis (very significant association)

Question 6

The P value can tell us the association of something occurring by chance. What does it not measure?

Answer 6

P value does not measure the strength of an association relationship

Question 7

What can P value be affected by?

Answer 7

• Can be affected by sample size: the bigger the size, the lower the P value, even under same frequency
• Can be affected by allele frequency

Question 8

What is the measure of strength?

Answer 8

Odds ratio
- Increased risk for a phenotype by carrying a specific genotype/allele compared to pt w/o carrying

Question 9

What is the equation of odds ratio?

Answer 9

OR = (odds of phenotype in an individual w the genotype/allele)/(odds of phenotype in an individual w/o genotype/allele)

Question 10

How is odds ratio calculated?

Answer 10

Example from lecture

Question 11

What does OR=1 mean?

Answer 11

No association

Question 12

What does OR>1 mean?

Answer 12

Potentially increases the risk (the allele will be called “risk allele”). The greater the OR is, the higher the risk the allele will confer to phenotype

Question 13

What does OR<1 mean?

Answer 13

Potentially decreases the risk (the allele will be called “protective allele”). The smaller the OR is, the lower risk the allele will confer to phenotype.

Question 14

What does 95% CI greater than 1 mean?

Answer 14

There is a significant risk effect

Question 15

What does 95% CI containing 1 mean?

Answer 15

There is no statistical significance

Question 16

What does 95% CI less than 1 mean?

Answer 16

There is a significant protective effect

Question 17

Why must there be a correction for P values?

Answer 17

Due to large number of tests done for many SNPs vs the single phenotype, there will be a much higher probability to have many SNPs associated with phenotype just by chance (FALSE POSITIVE) [called multiple-testing]

Question 18

How are P values corrected to account for false positives?

Answer 18

Bonferroni correction: corrected P = 0.05/N
- N: total number of SNPs tested

Question 19

What is the standard corrected significant GWAS P value?

Answer 19

5x10^-8

Question 20

What is key to doing experiments to test hypothesis?

Answer 20

Control (positive and negative control)

Question 21

What do human clinical trials often don’t have due to ethical reasons?

Answer 21

Negative control (compared to standard of care instead)

Question 22

What are essential to have reliable results, especially for human clinical trials?

Answer 22

• A large sample size
• Test one concept in multiple biological systems

Question 23

Knowing the distribution of your data is important. What do the majority of datasets we deal with do to do this?

Answer 23

Follow normal (Gaussian) distribution

Question 24

Clinical studies often use median, but not mean. Why?

Answer 24

Faster, patient data may not be normally distributed