ArticleGenetic epidemiology2019
A comparison of popular TDT-generalizations for family-based association analysis.
Article in Genetic epidemiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Intracellular protein GBF1 displays significant associations with amyloid pathology in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Bayesian polygenic risk estimation approach to nuclear families with discordant sib-pairs for myelomeningocele.PloS one · 2024Article
- Benchmarking statistical methods for analyzing parent-child dyads in genetic association studies.Genetic epidemiology · 2022Review
- Recent advances and challenges of rare variant association analysis in the biobank sequencing era.Frontiers in genetics · 2022Review
- A unifying framework for rare variant association testing in family-based designs, including higher criticism approaches, SKATs, and burden tests.Bioinformatics (Oxford, England) · 2021Article
- Candidate-gene association analysis for a continuous phenotype with a spike at zero using parent-offspring trios.Journal of applied statistics · 2020Article
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Authors and funding
3 authors.
Funding
Abstract
The transmission disequilibrium test (TDT) is the gold standard for testing the association between a genetic variant and disease in samples consisting of affected individuals and their parents. In practice, more complex pedigree structures, that is siblings with no parents, or three-generational pedigrees with possibly missing genotypes, are common. There are several generalizations of the TDT that are suitable for use with arbitrary pedigree structures. We consider three such frequently used generalizations, family-based association test, pedigree disequilibrium test, and generalized disequilibrium test, that have accompanying software and compare them regarding validity and power in the single variant setting. We use simulations to study the effects of population admixture, populations whose genotypes are not in Hardy-Weinberg equilibrium (HWE), different pedigree structures, and the presence of linkage. Whereas our results show that some TDT generalizations can have a substantially increased Type 1 error, these tests are often used in substantive research without caveats about the validity of their Type 1 error. For the association analysis of rare variants in sequencing studies, region-based extensions of the TDT generalizations, that rely on the postulated robustness of the single variant tests, have been proposed. We discuss the implications of our results for these region-based extensions.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.