A simple and robust TDT-type test against genotyping error with error rates varying across families

K. F. Cheng, J. H. Chen

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

The transmission/disequilibrium test (TDT), a family based test of linkage and association, is a popular test for studies of complex inheritance, as it is nonparametric and robust against spurious conclusions induced by hidden genetic structure, such as stratification or admixture. However, the TDT may be biased by genotyping errors. Undetected genotyping errors may be contributing to an inflated type I error rate among reported TDT-derived associations. To adjust for bias, a popular approach is to assume a genotype error model for describing the pattern of errors and propose association tests using likelihood method. However, all model-based approaches tend to perform unsatisfactorily if the related genotyping error rates are not identical across all families. In this paper, we propose a TDT-type association test which is not only simple, robust against population stratification (and hence the assumption of Hardy-Weinberg equilibrium is not required), but also robust against genotyping error with error rates varying across families. Simulation studies confirm that the new test has very reasonable performance.

Original languageEnglish
Pages (from-to)114-122
Number of pages9
JournalHuman Heredity
Volume64
Issue number2
DOIs
Publication statusPublished - May 2007
Externally publishedYes

Keywords

  • Genotyping error
  • Population stratification
  • Robustness
  • Transmission/ disequilibrium test

ASJC Scopus subject areas

  • Genetics(clinical)

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