Transmission/disequilibrium test when neither parent is available in some families: A non-iterative approach
Journal
Journal of Cancer Epidemiology and Prevention
Journal Volume
7
Journal Issue
2
Pages
97-103
Date Issued
2002
Author(s)
Abstract
Background. The transmission/disequilibrium test (TDT) is a simple method of detecting linkage between a marker locus and a disease-susceptibility locus. The test requires genotype data from the affected individuals (the probands) and their parents, the 'case-parents triads'. However, missing data from parents often complicate the situations. Several non-iterative methods, such as the sibling-based TDT, the reconstruction-combined TDT, and the 1-TDT have been proposed to deal with the problem. But when the father, the mother, and other non-proband siblings in a family are all unavailable for study, that family has to be excluded from analysis by any of the above methods. Methods. The author proposes a new non-iterative method to deal with the situation when the data contain some 'orphaned' probands. The method utilises the complete data from case-parents triads to infer probabilistically the missing parental genotypes, under the assumption that the missingness is independent of genotype and ethnic origin. The methods can be tailored to specific genetic models, such as the gene-dose, dominance, and recessive alternatives. Results. Simulation analysis shows that, under the null hypothesis of no linkage, the proposed method is not prone to produce an excess of false positive results, even in complex situations such as population stratification or assortive mating. Under the linkage alternative, the new method recaptures much of the information that would be lost by discarding the orphaned probands. Discussion. The method provides a way for dealing with the situation where neither parents nor siblings are available in a TDT study.
Subjects
Epidemiologic methods; Genetics; Linkage analysis; Missing data; Recombination fraction; Transmission/disequilibrium test
SDGs
Other Subjects
analytical error; article; assortative mating; controlled study; dominant gene; ethnology; family study; gene dosage; gene linkage disequilibrium; genetic linkage; genetic model; genotype; hypothesis; inheritance; methodology; parent; population research; probability; process model; recessive gene; stratification; algorithm; biological model; chromosome map; genetic predisposition; genetics; human; Monte Carlo method; parent; Algorithms; Chromosome Mapping; Genetic Predisposition to Disease; Genotype; Humans; Linkage Disequilibrium; Models, Genetic; Monte Carlo Method; Parents
Publisher
Martin Dunitz Ltd
Type
journal article