Genetic Associations: The Power of the Transmission/Disequilibrium Test

The Transmission/Disequilibrium Test (TDT) is a statistical method used in genetic studies to test for linkage and association between genetic markers and diseases or traits. It was originally developed to address the issue of population stratification, which can lead to false-positive results in association studies. The TDT uses family data, typically parent-offspring trios, to assess whether a particular allele is transmitted from heterozygous parents to affected offspring more frequently than expected by chance.

In the context of case-control studies, the TDT can be adapted to test for differential transmission of an allele from heterozygous parents to affected offspring. The null hypothesis of the TDT is that there is no differential transmission, which is tested by comparing the observed transmission rate to the expected rate under Mendelian inheritance. This test can be performed using various statistical methods, such as the Monte-Carlo method or permutation tests, to account for different genetic models and population structures​​.

The TDT is particularly useful in the presence of population stratification, where subpopulations have different allele frequencies. In such cases, the TDT can be modified to account for the stratification by adjusting the transmission probabilities based on the subpopulation structure. This allows for a more accurate assessment of the genetic association while controlling for potential confounding due to population stratification​​.

In practical applications, the TDT has been used in various genetic studies, such as the analysis of whole genome data in childhood-onset systemic lupus erythematosus (SLE). In this context, the TDT can help identify genetic variants associated with the disease by comparing the transmission of alleles from parents to affected children​​.

Overall, the TDT is a valuable tool in genetic epidemiology, providing a robust method for testing genetic associations while controlling for potential confounders like population stratification. Its application in various genetic studies continues to contribute to our understanding of the genetic basis of complex diseases and traits.

Reference:

Ruiz-Narváez, E. A., & Campos, H. (2004). Transmission disequilibrium test (TDT) for case–control studies. European journal of human genetics, 12(2), 105-114.
Sebro, R., & Rogus, J. J. (2010). The power of the Transmission Disequilibrium Test in the presence of population stratification. European Journal of Human Genetics, 18(9), 1032-1038.
Vazzana, K. M., Musolf, A. M., Bailey-Wilson, J. E., Hiraki, L. T., Silverman, E. D., Scott, C., ... & Lewandowski, L. B. (2023). Transmission disequilibrium analysis of whole genome data in childhood-onset systemic lupus erythematosus. Genes & Immunity, 24(4), 200-206.