Transmission disequilibrium test
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In population genetics, the transmission disequilibrium test (TDT) was proposed by Spielman, McGinnis & Ewens (1993) as a family-based association test to compare transmission frequencies of an allele thought to be associated with a disease and its alternate allele using affected children born to parents heterozygous for the allele.
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| M1 | M2 | total | ||
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![m(1-m)+\left[\frac{(1-\theta-m)\delta}{p}\right]](../../../math/8/5/5/8558b42fca0313f212b68fb5949365bb.png) |
![m+\left[\frac{(1-\theta)\delta}{p}\right]](../../../math/a/6/c/a6c7c1bd9430b4c362bcebd814f90d19.png) |
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| Transmitted allele | M2 | ![m(1-m)+\left[\frac{(\theta-m)\delta}{p}\right]](../../../math/5/0/4/504ddc5a03edcad93e3e5382a0854c0d.png) |
![(1-m)^2-\left[\frac{(1-m)\delta}{p}\right]](../../../math/4/8/1/4814f7eb0e5508b14cd392bdf8d07a07.png) |
![1-m-\left[\frac{(1-\theta)\delta}{p}\right]](../../../math/a/b/2/ab2af6b5f624bcbd9b6416d92a9c8e81.png) |
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Stratification by parental mating type Wittkowski & Liu (2002) adjusts for a problem also seen in case-control association tests Sasieni (1997) namely that, due to the same confounders affecting penetrance, the effects of the two alleles transmitted to the same child are not independently observed, even though the alleles are independently transmitted.
[edit] References
- Ewens WJ, Spielman RS. (2005) What Is the Significance of a Significant TDT? Hum Hered. 60(4):206-10.
- Wittkowski KM, Liu X. (2002/2004) A statistically valid alternative to the TDT Hum Hered. 54(3):157-64. Comment, author reply, discussion Hum Hered. 58(1):59-62.
- Spielman RS, Ewens WJ. (1998) A sibship test for linkage in the presence of association: the sib transmission/disequilibrium test. Am J Hum Genet. 62(2):450-8.
- Sasieni PD. (1997) From genotypes to genes: doubling the sample size. Biometrics. 53 (4):1253-61.
- Spielman RS, Ewens WJ. (1996) The TDT and other family-based tests for linkage disequilibrium and association. Am J Hum Genet 59:983-9
- Ewens WJ, Spielman RS. (1995) The transmission/disequilibrium test: history, subdivision, and admixture. Am J Hum Genet. 57(2):455-64.
- McGinnis RE, Ewens WJ, Spielman RS. (1995) The TDT reveals linkage and linkage disequilibrium in a rare disease. Genet Epidemiol. 12(6):637-40.
- Spielman RS, McGinnis RE, Ewens WJ. (1993) Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM). Am J Hum Genet. 52(3):506-16.
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