复旦大学医学遗传学casecontrolTDT分析

Indirect Tests
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 genetic association analyses • Direct versus indirect association • Indirect association: marker-based disease association – Exploits LD between markers and unFra Baidu bibliotekbserved disease variants • Examples of direct and indirect association studies • Study designs for direct and marker-based (LD) association
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
Fudan Genetic Workshop 2005 Genetic Epidemiology in Populations
Genetic Association Studies: Studies with Unrelated Individuals
Yin Yao
yyao@jhsph.edu
Fudan Genetic Workshop, Jan 04 2005
APOE gene on c19
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Rely on correlation (LD) between these alleles to detect association!
Direct Tests
• Test for association between observed genotypes and disease outcome
Genetic Association Studies in Epidemiology
Applications: • • • • • Fine mapping Candidate gene effects Whole genome scan Gene – environment effects Drug response modification
• 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
APOE gene on c19
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• Genotype that particular site for association study
Genetic epidemiology studies – two different concepts
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• Directly measure potentially predisposing alleles
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 Eg: Genotype a nearby genetic marker among study participants
Genetic epidemiology studies – two different concepts
1. Direct method – Testing whether a particular allele is a disease predisposing (causative) allele – ‘exposure status’ directly measured Eg: A particular APOE allele (e4) changes protein isoform