A transmission disequilibrium test for general pedigrees that is robust to the presence of random genotyping errors and any number of untyped parents

Derek Gordon, Chad Haynes, Christopher Johnnidis, Shailendra B. Patel, Anne M. Bowcock, Jürg Ott

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

Two issues regarding the robustness of the original transmission disequilibrium test (TDT) developed by Spielman et al are: (i) missing parental genotype data and (ii) the presence of undetected genotype errors. While extensions of the TDT that are robust to items (i) and (ii) have been developed, there is to date no single TDT statistic that is robust to both for general pedigrees. We present here a likelihood method, the TDTae, which is robust to these issues in general pedigrees. The TDTae assumes a more general disease model than the traditional TDT, which assumes a multiplicative inheritance model for genotypic relative risk. Our model is based on Weinberg's work. To assess robustness, we perform simulations. Also, we apply our method to two data sets from actual diseases: psoriasis and sitosterolemia. Maximization under alternative and null hypotheses is performed using Powell's method. Results of our simulations indicate that our method maintains correct type I error rates at the 1, 5, and 10% levels of significance. Furthermore, a Kolmorogov-Smirnoff Goodness of Fit test suggests that the data are drawn from a central χ 2 with 2 df, the correct asymptotic null distribution. The psoriasis results suggest two loci as being significantly linked to the disease, even in the presence of genotyping errors and missing data, and the sitosterolemia results show a P-value of 1.5 × 10-9 for the marker locus nearest to the sitosterolemia disease genes. We have developed software to perform TDTae calculations, which may be accessed from our ftp site.

Original languageEnglish (US)
Pages (from-to)752-761
Number of pages10
JournalEuropean Journal of Human Genetics
Volume12
Issue number9
DOIs
StatePublished - Sep 1 2004
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Keywords

  • Genetics
  • Misclassification
  • Statistics

Fingerprint Dive into the research topics of 'A transmission disequilibrium test for general pedigrees that is robust to the presence of random genotyping errors and any number of untyped parents'. Together they form a unique fingerprint.

  • Cite this