Association Analysis.pptVIP

Association Analysis SeattleSNPs March 21, 2006 Analyzing SNP Data Study Design SNPs vs Haplotypes Regression Analysis Population Structure Multiple Testing Whole Genome Analysis Analyzing SNP Data Study Design SNPs vs Haplotypes Regression Analysis Population Structure Multiple Testing Whole Genome Analysis Study Design Heritability Prior hypotheses Target phenotype(s) Power Ethnicity Replication Heritability Is your favorite phenotype genetic? Heritability (h2) is the proportion of variance attributed to genetic factors h2 ~ 100%: ABO Blood type, CF h2 80%: Height, BMI, Autism h2 50-80%: Smoking, Hypertension, Lipids h2 20- 50%: Marriage, Suicide, Religiousness h2 ~ 0: ?? Prior Hypotheses There will always be too much data There will (almost) always be priors Favored SNPs Favored Genes Make sure you’ve stated your priors (if any) explicitly BEFORE you look at the data Target Phenotypes Statistical Power Null hypothesis: all alleles are equal risk Given that a risk allele exists, how likely is a study to reject the null? Are you ready to genotype? Genetic Relative Risk Power Analysis Statistical significance Significance = p(false positive) Traditional threshold 5% Statistical power Power = 1- p(false negative) Traditional threshold 80% Traditional thresholds balance confidence in results against reasonable sample size Small sample: 50% Power Maximizing Power Effect size Larger relative risk = greater difference between means Sample size Larger sample = smaller SEM Measurement error Less error = smaller SEM Large sample: 97.5% Power Risk Allele Example10% Population Frequency Homozygous Relative Risk = 4 Multiplicative Risk Model Het RR = 2 Case Freq 18.2% Control Freq 9.9% Homozygous Relative Risk = 2 Multiplicative Risk Model Het RR = 1.4 Case Freq 13.6% Control Freq 9.96% Power to Detect RR=2N Cases, N Controls Power to Detect RR=2N Cases, N Controls Power to Detect RR=2N Cases, N Controls Power to Detect RR=2N Cases, N Controls Power to Detect SN