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: Population-based (controls = general pop) Family-based (controls = genetic relatives)

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

FAD: Family-based Association Design Genotype: Number of A alleles: Difference: (1) (2) (3) (4) (3) – (4) Family: Sz Sib Normal Sib Smith AA Aa 2 1 Jones … Zorks aa Mean: X =

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

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

TDT: Transmission Disequilibrium Test Aa aa ?a 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.