design association study with hapmap.pptVIP

Goals of this segment Briefly summarize HapMap design and current status Discuss the application of HapMap to all aspects of association study design, analysis and interpretation HapMap Project High-density SNP genotyping across the genome provides information about SNP validation, frequency, assay conditions correlation structure of alleles in the genome HapMap Samples 90 Yoruba individuals (30 parent-parent-offspring trios) from Ibadan, Nigeria (YRI) 90 individuals (30 trios) of European descent from Utah (CEU) 45 Han Chinese individuals from Beijing (CHB) 45 Japanese individuals from Tokyo (JPT) HapMap progress ENCODE-HAPMAP variation project Ten “typical” 500kb regions 48 samples sequenced All discovered SNPs (and any others in dbSNP) typed in all 270 HapMap samples Current data set – 1 SNP every 279 bp Completeness of dbSNP Recombination hotspots are widespreadand account for LD structure Utility of LD in association study “If I’m a causal variant, what is relevant to my detection in association studies is how well correlated I am with one of the SNPs or haplotypes examined in the study.” Coverage of Phase II HapMap(estimated from ENCODE data) Coverage of Phase II HapMap(estimated from ENCODE data) Coverage of Phase II HapMap(estimated from ENCODE data) Coverage of Phase II HapMap(estimated from ENCODE data) Applying the HapMap Study design - tagging Study coverage evaluation Study analysis - improving association testing Study interpretation Comparison of multiple studies Connection to genes/genomic features Integration with expression and other functional data Other uses of HapMap data Admixture, LOH, selection Tagging from HapMap Since HapMap describes the majority of common variation in the genome, choosing non-redundant sets of SNPs from HapMap offers considerable efficiency without power loss in association studies Pairwise tagging Pairwise Tagging Efficiency Use of haplotypes can improve genotyping efficiency Efficiency and power How to