Transmission-disequilibrium test

One conventional approach that tackles the confounding effect is family-based design. A typical family-based design involves genetic information for both parents and an affected child. A transmission disequilibrium test (TDT) can be used to examine the association of an allele with a phenotype by testing whether the allele is over- or undertransmitted to the affected offspring with a statistic (12). 

In response to the biases inherent in case-control studies, family-based studies utilizing the transmission/ disequilibrium test (TDT) have become the gold standard in detection of association (Thomson, 1995 Spielman and Ewens, 1996). The family-based studies require analysis of alleles of both parents and the affected individual to determine which of the parental alleles are transmitted to the affected individual. Only data from heterozygous parents are informative and, for a two-allele system, each allele has an expected transmission rate of 50%. 

Allison, D.B. (1997). Transmission-disequilibrium tests for quantitative traits. Am J Hum Genet 60 676-690. 

Waldman, I.D., Robinson, B.E, and Feigon, S.A. (1997) Linkage disequilibrium between the dopamine transporter gene (DATl) and bipolar disorder extending the transmission disequilibrium test (TDT) to examine genetic heterogeneity. Genet Epidemiol 14(6) 699-704. 

Genetic association studies may be either family based, or population based (26,27). Family based studies can use transmission disequilibrium tests (TDT), a test that detects association in the presence of linkage. Population-based tests use analysis of variance (ANOVA) among multiple subgroups. The TDT was first proposed by Spielman and Ewens (28). The basic premise of the TDT is that certain alleles at a locus are disproportionately transmitted Irom parents to an affected offspring therefore the basic sampling unit for the TDT is a nuclear family with at least one affected offspring... 

A transmission disequilibrium test that does not require parental data has also been developed (56). The sib-TDT method uses the marker data from unaffected sibs instead of from parents, thus allowing application of the principle of the TDT to sibships without parental data. 

Spielman RS, Ewens WJ. A sibship test for linkage in the presence of association the sib transmission/disequilibrium test. Am J Hum Genet 1998 62(2) 450-458. 

Sun F, Flanders WD, Yang Q, Khoury MJ. Transmission disequilibrium test (TDT) when only one parent is available the 1-TDT. Am J Epidemiol 1999 150 97-104. 

Lin S, Chakravarti A, Cutler DJ. 2004. Exhaustive allelic transmission disequilibrium tests as a new approach to genome-wide association studies. Nat Genet 36 1181-1188. 

Kim SJ, Young LJ, Gonen D, Veenstra-VanderWeele J, Courchesne R, Courchesne E, Lord C, Leventhal BL, Cook EH, Jr., Insel TR (2002) Transmission disequilibrium testing of arginine vasopressin receptor lA (AVPRIA) polymorphisms in autism. Mol Psychiatry 7 503-507. 

QTDT (Quantitative Trait Transmission Disequilibrium Test)... 

Several studies using the transmission/disequilibrium test to determine whether SLC6A4 contributes to autism failed to reveal any reliable proof... 

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