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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:
(1) Population-based (controls = general pop)
(2) Family-based (controls = genetic relatives)
Population-based
Association Design
Genotype:
AA
Aa
Schiz:
Phenotype:
Not Schiz:
Do c2 test for association.
aa
FAD: Family-based
Association Design
Genotype:
Number of A alleles:
Difference:
(3) – (4)
(1)
(2)
(3)
(4)
Family:
Sz Sib
Normal Sib
Sz Sib
Normal
Sib
Smith
AA
Aa
2
1
1
Jones
Aa
Aa
1
1
0
…
…
…
…
…
…
Zorks
AA
aa
2
0
2
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:
1. Select families with affected offspring.
2. Genotype parents on the gene.
3. (Select informative matings).
4. Genotype offspring.
5. Test whether transmission of allele = .5
TDT: Transmission Disequilibrium Test
Informative:
Aa
aa
Aa
?a
Not Informative:
AA
AA
AA
AA
?A
Aa
Aa
??
aa
?A
aa
aa
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.