Fernando Rivadeneira Genetic Laboratory Association testing - PowerPoint PPT Presentation

Fernando Rivadeneira Genetic Laboratory

Association testing • Compare the allele distribution between cases and controls • Only the markers that are close to a true risk increasing allele will be overrepresented in patients • Only the markers that are close to a protective risk increasing allele will be underrepresented in patients

Error rate Research True relationship Finding yes no Power = + (association) type 1 error 1- beta Alpha/p-value - (no association) type 2 error beta

Comparing odds ratios for true risk allele and marker (r2=0.80) True risk allele Marker Allele Proportion carriers 0.2 0.35 Odds ratio heterozygote 2 1.49 Odds ratio homozygote 4 2.27 Proportion carriers 0.2 0.35 Odds ratio heterozygote 1.5 1.24 Odds ratio homozygote 1.5 1.36

Adjustment for Multiple Testing Test1 Test2 ok ok 0.95 * 0.95=0.90 wrong ok 1-0.90=0.10 instead of 0.05 ok wrong wrong wrong Bonferroni adjustment p = 0.05/2, the joint probability of at least 1 false + is 1- (0.975 2 ) = 1 – 0.95 = 0.05 If you test 125 variants, then the joint probability of at least 1 false + is 1- (0.95 125 ) = 1 – 0.00 = 1 Bonferroni adjustment p = 0.05/125 = 4.0 x 10 -4