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Association Design

Association Design. Begins with KNOWN polymorphism theoretically expected to be associated with the trait (e.g., DRD2 and schizophrenia). Genotypes people on the gene and phenotypes them on the trait. Tests whether the genotype is associated with the trait. Two types:.

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Association Design

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  1. Association Design • Begins with KNOWN polymorphism theoreticallyexpected to be associated with the trait (e.g., DRD2 and schizophrenia). • Genotypes people on the gene and phenotypes them on the trait. • Tests whether the genotype is associated with the trait. • Two types: • Population-based (controls = general pop) • Family-based (controls = genetic relatives)

  2. Genotype: AA Aa aa Schiz: Phenotype: Not Schiz: Population-basedAssociation Design Do c2 test for association.

  3. X = FAD: Family-basedAssociation Design

  4. TDT: Transmission Disequilibrium Test • Type of FAD: • Many, many variations: All test whether transmission of an allele agrees / disagrees with Mendel’s law of segregation. • Example: • Select families with affected offspring. • Genotype parents on the gene. • (Select informative matings). • Genotype offspring. • Test whether transmission of allele = .5

  5. TDT: Transmission Disequilibrium Test Informative: Not Informative: Aa aa Aa AA AA Aa aa aa AA AA aa Aa ?? ?a ?A ?A

  6. Aa aa ?a TDT: Transmission Disequilibrium Test • If father transmits A > .50, A is the risk allele. • If father transmits A < .50, a is the risk allele. • If father transmits A = .50, no association.

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