Genetic Models and Other Genetic Tests
HelixTree will perform tests based upon one genetic model or other grouping of genetic information. These models and other genetic tests are as follows:
- Basic Allelic Tests
- Genotypic Tests
- Additive Model
- Dominant Model
- Recessive Model
These are described in the following subsections.
18.2.1 Basic Allelic Tests
For a basic allelic test, the genotypes dd, Dd, and DD are resolved into pairs of alleles d and d, D and d, or D and D. Both elements of each subject’s genotype are considered to correspond to the same value of the dependent variable. The associations with these individual alleles are then tested.
For example, the following case/control dependent variable and genetic variable columns
| Case/Control | Genotype |
|---|---|
| 0 | d_d |
| 1 | D_d |
| 1 | D_D |
would be translated to:
| Case/Control | Allele |
|---|---|
| 0 | d |
| 0 | d |
| 1 | D |
| 1 | d |
| 1 | D |
| 1 | D |
and the following quantitative phenotype dependent variable and genetic variable columns
| Phenotype | Genotype |
|---|---|
| 0.6 | d_d |
| 2.9 | D_d |
| 1.7 | D_D |
would be translated to:
| Phenotype | Allele |
|---|---|
| 0.6 | d |
| 0.6 | d |
| 2.9 | D |
| 2.9 | d |
| 1.7 | D |
| 1.7 | D |
The advantage of this test model is that the number of observations has been doubled.
The disadvantage is that the genotypic-specific information, such as which alleles are paired together, is ignored.
A further disadvantage of basic allele testing is that stratification correction through the Principal Components Analysis method is not available for this model.
18.2.2 Genotypic Tests
HelixTree “Genotypic Tests” refer to testing on the genotypes dd, DD, and Dd without regard to any “order” or allelic count or allelic pairing that they might have.
These tests can reveal associations without regard to any specific genetic model, even while it will not “hide” associations because of the model being “wrong”.
However, stratification correction through the Principal Components Analysis method is not available for this model. Also, no stratification correction is available at all for this model if the response is a quantitative trait.
18.2.3 Additive Model
Under this model, testing is designed specifically to reveal associations that depend additively upon the minor allele – that is, where having two minor alleles (DD) rather than having no minor alleles (dd) is twice as likely to affect the outcome in a certain direction as is having just one minor allele (Dd) rather than no minor alleles (dd).
NOTE: For a case/control response, two odds-ratio tests (see 18.3.6) are available under this model. These tests, which are really not a part of the additive model, as such, are not only indicators of the intensity of any association, but are also a check on the validity of the additive model itself in describing the effect.
18.2.4 Dominant Model
This model specifically tests the association of having at least one minor allele D (either Dd or DD) vs. not having it at all (dd).
18.2.5 Recessive Model
This model specifically tests the association of having the minor allele D as both alleles (DD) vs. having at least one major allele d (Dd or dd).
