Transmission disequilibrium test

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Transmission disequilibrium test


The Transmission Disequilibrium Test (TDT) is a statistical method used in genetics to determine whether a particular allele of a genetic marker is associated with a trait or disease. This method is particularly useful for studying complex genetic traits that do not follow simple Mendelian inheritance patterns. The TDT was introduced by Spielman, McGinnis, and Ewens in 1993 as a way to test for linkage disequilibrium while avoiding the confounding effects of population stratification that can affect case-control studies.

Overview[edit | edit source]

The Transmission Disequilibrium Test is based on the principle of testing for non-random transmission of alleles from parents to affected offspring. In essence, the TDT compares the frequency of alleles transmitted to affected offspring with the frequency of alleles not transmitted. If an allele is associated with a disease, it will be transmitted more often than expected by chance.

Methodology[edit | edit source]

The TDT is performed by analyzing trios, which consist of an affected child and both parents. For each trio, the genotype of the parents and the affected child is determined. The test focuses on heterozygous parents (parents who have two different alleles at the marker locus) because these parents can transmit either allele to their offspring. By comparing the allele transmitted to the affected child with the allele not transmitted, researchers can determine if there is preferential transmission of one allele.

Applications[edit | edit source]

The Transmission Disequilibrium Test has been widely used in genetic studies of complex diseases such as autism, schizophrenia, and bipolar disorder. It is particularly useful for diseases that are thought to have a genetic component but do not follow simple inheritance patterns. The TDT can help identify genetic markers associated with these diseases, which can lead to a better understanding of their genetic basis and potentially to the development of new treatments.

Advantages[edit | edit source]

One of the main advantages of the TDT is its robustness to population stratification. Unlike case-control studies, which can be biased by differences in allele frequencies between populations, the TDT compares alleles within families, thus controlling for population structure. Additionally, the TDT does not require a large sample size, making it a cost-effective option for genetic studies.

Limitations[edit | edit source]

However, the TDT has some limitations. It can only be used with family data, requiring the availability of genotyped parents and affected offspring. This requirement can limit the applicability of the TDT in situations where parental genotypes are not available. Furthermore, the TDT is less powerful for detecting genes with small effects on disease risk compared to some other methods.

Conclusion[edit | edit source]

The Transmission Disequilibrium Test remains a valuable tool in the field of genetic research, particularly for studying complex diseases with a genetic component. Its ability to control for population stratification and its applicability to diseases with complex inheritance patterns make it a unique and powerful method for identifying genetic associations.

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Contributors: Prab R. Tumpati, MD