9 - Drug Discovery 1 Flashcards
How do you calculate the # of alleles from the number of genotypes in a case control study?
What is the interpretation of P>0.1?
No presumption against null hypothesis (no significant association)
What is the interpretation of 0.05<P<0.1?
Low presumption against null hypothesis (marginal association)
What is the interpretation of P<0.05?
Strong presumption against null hypothesis (marginal association)
What is the interpretation of P<0.01?
Very strong presumption against null hypothesis (very significant association)
The P value can tell us the association of something occurring by chance. What does it not measure?
P value does not measure the strength of an association relationship
What can P value be affected by?
- 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
What is the measure of strength?
Odds ratio
- Increased risk for a phenotype by carrying a specific genotype/allele compared to pt w/o carrying
What is the equation of odds ratio?
OR = (odds of phenotype in an individual w the genotype/allele)/(odds of phenotype in an individual w/o genotype/allele)
How is odds ratio calculated?
Example from lecture
What does OR=1 mean?
No association
What does OR>1 mean?
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
What does OR<1 mean?
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.
What does 95% CI greater than 1 mean?
There is a significant risk effect
What does 95% CI containing 1 mean?
There is no statistical significance
What does 95% CI less than 1 mean?
There is a significant protective effect
Why must there be a correction for P values?
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]
How are P values corrected to account for false positives?
Bonferroni correction: corrected P = 0.05/N
- N: total number of SNPs tested
What is the standard corrected significant GWAS P value?
5x10^-8
What is key to doing experiments to test hypothesis?
Control (positive and negative control)
What do human clinical trials often don’t have due to ethical reasons?
Negative control (compared to standard of care instead)
What are essential to have reliable results, especially for human clinical trials?
- A large sample size
- Test one concept in multiple biological systems
Knowing the distribution of your data is important. What do the majority of datasets we deal with do to do this?
Follow normal (Gaussian) distribution
Clinical studies often use median, but not mean. Why?
Faster, patient data may not be normally distributed
