复旦大学医学遗传学课件case_control_TDT分析.ppt

Fudan Genetic Workshop 2005Genetic Epidemiology in Populations Yin Yao yyao@jhsph.edu Fudan Genetic Workshop, Jan 04 2005 Assessing risk for disease due to specific alleles/genotypes Contrast direct / indirect genetic association studies Discuss genetic models Tests and estimates of association between alleles/genotypes and disease Designs to be used Learning Objectives for This Lecture Applications for genetic association analyses Direct versus indirect association Indirect association: marker-based disease association Exploits LD between markers and unobserved disease variants Examples of direct and indirect association studies Study designs for direct and marker-based (LD) association Genetic Association Studies in Epidemiology Applications: Fine mapping Candidate gene effects Whole genome scan Gene – environment effects Drug response modification Genetic Association Studies in Epidemiology Common Designs: Cross-sectional Case-control Cohort Clinical Trial (drug response hypothesis is really a case-control) Case-family (trios, sibs, extended families) Case-only Learning Objectives for This Lecture Applications for association analyses Direct versus indirect association Indirect association: marker-based association Exploits LD Examples of direct and indirect association studies Study designs for direct and marker-based (LD) association Direct method Testing whether a particular allele is a disease - predisposing (causative) allele ‘exposure status’ directly measured 2. ‘LD Mapping’ (indirect method) ‘exposure status’ not directly measured Rely on markers correlated with true exposure status This correlation is due to linkage disequilibrium Direct Tests Test for association between observed genotypes and disease outcome Indirect Tests Test for association between marker genotypes and disease outcome Direct Method: Candidate Allele Testing Must know potentially functional polymorphisms SNPs may offer set of candidate loci for this method Eg, look a