Lecture #9

Question 1

Case control study

Answer 1

convert the # of genotypes into # of alleles
T/T * 2 + T/C = observed # of T

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 null hypothesis (marginal association)

Question 4

P<0.05

Answer 4

strong presumption against null hypothesis (significant association)

Question 5

P<0.01

Answer 5

very strong presumption against null hypothesis (very significant association)

Question 6

P value does not measure

Answer 6

strength of an association relationship
can be affected by sample size - bigger the size, lower the P value
can be affected by allele freqeuncy

Question 7

Measure of the strength

Answer 7

odds ratio: increased risk for a phenotype by carrying a specific genotype/allele compared to the pts without carrying
OR = odds of phenotype in an individual with the genotype/allele / odds of phenotype in an individual without the genotype/allele
hazard ratio is a similar concept, but is mainly discussed in survival data

Question 8

OR = 1

Answer 8

no association

Question 9

OR > 1

Answer 9

potentially increases the risk

Question 10

OR < 1

Answer 10

potentially decreases the risk

Question 11

95% confidence interval

Answer 11

over 95% of probability that the association is confident
like the p value for x^2, 95% CI is a statistical probability for OR (standard error of OR)

Question 12

if 95% CI is greater than 1

Answer 12

there is a significant risk effect

Question 13

if 95% CI contains 1

Answer 13

no statistical significance

Question 14

if 95% CI is less than 1

Answer 14

there is a significant protective effect

Question 15

Correction for P values

Answer 15

due to large # of tests for many SNPs vs the single phenotype, there will be much higher probability to have many SNPs associated with the phenotype just by chance (false positive) so called multiple testing
more SNPs tested, higher the probability for false positive

Question 16

Bonferroni correction

Answer 16

corrected P=0.05/N (total # of SNPs tested)
5x10^-8 as corrected significant GWAS P value

Question 17

Doing experiments to test your hypothesis

Answer 17

control is the key (positive control, negative control)
human clinical trials often don’t have negative control due to ethical reasons (compare to standard of care)
know the dynamic range of your data set (upper limit and lower limit)
to have reliable results (especially for the human clinical trials, a large sample size is essential)

Question 18

Know the distribution of your data

Answer 18

majority of the dataset we are dealing with follows normal (gaussian) distribution
clinical study often uses median but not mean - two reasons, faster and pt data may not be normally distributed)
test one concept in mutliple biological systems (molecular, cellular, rodents, human iPSCs) will make your conclusion more reliable