复旦大学医学遗传学casecontroltdt分析.pptxVIP

Fudan Genetic Workshop 2005Genetic Epidemiology in Populations ;Fudan Genetic Workshop, Jan 04 2005;Learning Objectives for This Lecture;Genetic Association Studies in Epidemiology;Genetic Association Studies in Epidemiology;Learning Objectives for This Lecture;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;Indirect Tests;;Indirect Method: LD Gene Mapping;Indirect Association Studies in Epidemiology;Localization;Indirect Association Studies in Epidemiology;Source: Uhl et al, 2001. AJHG 69:1290-1300.;Indirect Association Studies in Epidemiology;Candidate gene LD studies;Candidate gene LD studies;Candidate gene LD studies;Genotype-level tests for disease association;Ex: Alzheimer’s disease and APOE SNPs…;Modeling issues;Modeling issues;Logistic regression;Indirect Association Studies in Epidemiology;Ex: TGFa and oral clefts;Ex: TGFa and oral clefts;Ex: Incorporation of Environment;Ex: Incorporation of Environment;Logistic regression with interaction;Interpretations of Indirect Association Studies;Learning Objectives for This Lecture;;Choice of Design and Analysis;Study Designs for LD Mapping Strategies;Contrasts between epidemiologic and family-based association designs;Designs for LD studies of unrelated individuals;Study Designs used for LD mapping;Study Designs used for LD mapping;Case-Control;Study Designs used for LD mapping;1) Adjustment in Analysis Assess and correct for possible stratification Genomic control (Devlin and Roeder, 1999, Genomic Control for association studies. Biometrics, 1999. 55: p. 997-1004) Cluster analysis of genetic substructure based on markers (STRUCTURE, Pritchard et al. Inference of population structure using multilocus genotype data. Genetics, 2000. 155(2):