Relationship Between Case-Control Studies and the transmission/disequilibrium Test

Genet Epidemiol. 2000 Oct;19(3):193-201. doi: 10.1002/1098-2272(200010)19:3<193::AID-GEPI1>3.0.CO;2-2.


Case-control studies provide a powerful approach for detecting disease susceptibility loci that have only a weak to moderate impact on the risk of disease, or markers that are in linkage disequilibrium with such loci. However, since any association detected in a case-control study may result from uncontrolled confounding, evidence for disease-marker associations obtained from such studies must be confirmed by alternative methods. Since studies that use the transmission/disequilibrium test or TDT are frequently employed to confirm disease-marker associations detected in case-control studies, data are increasingly available from both case-control studies and "TDT studies" of the same disease-marker association. It would, therefore, be useful to have a single measure of the magnitude of the disease-marker association that would allow for comparison of results from these two study designs. Such a measure could also be used to estimate minimum sample size requirements for TDT studies of previously reported disease-marker associations. An obvious measure of the disease-marker association in TDT studies is the frequency (T) with which heterozygous parents transmit the putative, high-risk marker allele to affected offspring. In this paper, it is shown that T can also be estimated from case-control data with a minimum of assumptions, and that T is the critical parameter for determining power and estimating sample sizes for the TDT.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Validation Study

MeSH terms

  • Case-Control Studies*
  • Confounding Factors, Epidemiologic
  • Data Interpretation, Statistical*
  • Epidemiologic Research Design
  • Gene Frequency / genetics*
  • Genetic Markers / genetics*
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Heterozygote
  • Humans
  • Linkage Disequilibrium / genetics*
  • Risk Factors
  • Sample Size


  • Genetic Markers