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Strategies for Gene Discovery
Published in Thomas R. O’Brien, Chemokine Receptors and AIDS, 2019
The transmission disequilibrium test (TDT) (8) eliminates the problem of population substructure. The TDT uses the genetic data from parents of the affected individual to determine which allele was transmitted to the affected individual and which was not. Only parents who are heterozygous for the locus of interest are included in the analysis. The null hypothesis is that there will be an equal probability for transmission of each allele. Variants on the TDT test allow the use of siblings or other relatives instead (in addition to) of the parents (9). The disadvantage of the TDT is, of course, the need to collect specimens from relatives of the patients.
A Genetic Framework for Addiction
Published in Hanna Pickard, Serge H. Ahmed, The Routledge Handbook of Philosophy and Science of Addiction, 2019
Philip Gorwood, Yann Le Strat, Nicolas Ramoz
The transmission disequilibrium test (TDT) is another statistical method used in association studies, which takes into account families whose parents are heterozygous for the genetic marker studied. The TDT measures an excess allele transmission from parents to affected offspring, compared with the distribution due to chance, when that chance would be one in two. The main limitation of the TDT is the mandatory use of complete families, or trios at minimum, because families missing a parent introduce bias. To solve this problem, a TDT of sibling pairs was designed (Sibs-TDT and S-TDT). The S-TDT compares allele frequencies among dependent children with siblings to those unaffected, to measure the difference (the discordant pairs to share the susceptibility allele less frequently than if this was due to chance alone). Since some complex pathologies, like substance use disorders, may be better described as a continuous variable, from normal (abstinence or recreative use) to the most severe form of addiction, an association test for quantitative traits (Quantitative-TDT) was established. Finally, the intrinsic information for families, such as their overall size, whether or not they contain a particularly large set of siblings, or whether or not they are extended so as to include several generations and/or cousins, was also taken into consideration in the siblings disequilibrium test (Pedigree Disequilibrium Test) or in software such as FBAT (Family-Based Association Test).
Family-Based Case-Control Approaches to Study the Role of Genetics
Published in Ørnulf Borgan, Norman E. Breslow, Nilanjan Chatterjee, Mitchell H. Gail, Alastair Scott, Christopher J. Wild, Handbook of Statistical Methods for Case-Control Studies, 2018
Clarice R. Weinberg, Min Shi, David M. Umbach
An alternative and closely related approach to testing, which is also widely used, enumerates transmissions from informative, i.e., heterozygous, parents to affected offspring. Let b be the number of heterozygous parents who transmitted the a allele and c be the number who instead transmitted the A allele. The transmission disequilibrium test (TDT) (Spielman et al., 1993) is a McNemar’s test:(For each triad where transmission is ambiguous because both parents and the affected offspring are heterozygous, one adds 0.5 to b and 0.5 to c.) Under the null and with large numbers of informative families, the TDT statistic is distributed as chi-squared with 1 degree of freedom. Several extensions have been proposed to the TDT (Gordon et al., 2004); Spielman.Ewens.1998.
Influence of IL15 gene variations on the clinical features, treatment response and risk of developing childhood acute lymphoblastic leukemia in Latvian population
Published in Pediatric Hematology and Oncology, 2018
Dmitrijs Rots, Madara Kreile, Sergejs Nikulshin, Zhanna Kovalova, Linda Gailite
For the purpose of assessing the association of genetic variations in IL15 with the risk of developing ALL, a case–control, family–based association study and combined hybrid analysis were performed. Chi-square and Fisher's exact tests were used for the case–control association study and the transmission disequilibrium test (TDT) was carried out for the family based association study. All tests were performed as implemented in PLINK v1.07. [16] The haplotype combinations single-dose and double-dose effects was analysed using Haplin package 5.5 for R software which use hybrid analysis method to combine both of the study designs to increase the statistical power. [17] The SNV linkage disequilibrium (LD) was calculated using the Haploview software. [18] The p value < 0.05 was considered statistically significant.
Candidate-gene association analysis for a continuous phenotype with a spike at zero using parent-offspring trios
Published in Journal of Applied Statistics, 2020
Nadja Klein, Andrew Entwistle, Albert Rosenberger, Thomas Kneib, Heike Bickeböller
For quantitative traits, a number of quantitative TDT/FBAT versions exist [1,2,7,14,16, 20,21,23,27] for a review see [6]. Here we focus on the quantitative transmission disequilibrium test with mating type indicator (8]. 8]. n parent-offspring trios. The offspring phenotype
Choline acetyltransferase may contribute to the risk of Tourette syndrome: Combination of family-based analysis and case–control study
Published in The World Journal of Biological Psychiatry, 2018
Xiuling Yang, Wenmiao Liu, Mingji Yi, Ru Zhang, Yinglei Xu, Zuzhou Huang, Shiguo Liu, Tang Li
Statistical analyses were performed using the Statistical Package for Social Sciences 22.0. After examining the Hardy–Weinberg equilibrium, the allelic and genotypic frequencies between cases and controls were assessed by Chi-square test. The analysis of family data was performed using the transmission disequilibrium test (TDT) and haplotype relative risk (HRR), as well as the haplotype-based haplotype relative risk (HHRR).To increase the precision of the results, a Bonferroni’s correction test was carried out and P values <0.01 were considered significant.