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Genetics, Vol. 168, 2329-2337, December 2004, Copyright © 2004
doi:10.1534/genetics.103.025841
Robust Transmission/Disequilibrium Test for Incomplete Family Genotypes
Paola Sebastiani*,1,
Maria M. Abad
,
Gülhan Alpargu
and
Marco F. Ramoni
* Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts 02118
Software Engineering Department, University of Granada, Granada 18071, Spain
Department of Mathematics and Statistics, University of Massachusetts, Amherst, Massachusetts 01003
Children's Hospital Informatics Program and Harvard Partners Center for Genetics and Genomics, Harvard Medical School, Boston, Massachusetts 02115
1 Corresponding author: Department of Biostatistics, Boston University School of Public Health, 715 Albany St., Boston, MA 02118.
E-mail: sebas{at}bu.edu
Several solutions have been proposed to extend the transmission disequilibrium test (TDT) to include cases with missing parental genotype. However, completion of the missing parental genotype may bias the test if the underlying missing data mechanism is informative. Furthermore, all these solutions resolve the problem of missing parental genotype, while offspring with missing genotypes are typically ignored. We propose here an extension to the TDT, called robust TDT (rTDT), able to handle incomplete genotypes on both parents and children and that does not rest on any assumption about the missing data mechanism. rTDT returns minimum and maximum values of TDT that are consistent with all the possible completions of the missing data. We also show that, in some situations, rTDT can achieve both greater power and greater significance than the popular TDT analysis of incomplete data. rTDT is applied to a database of markers of susceptibility to Crohn's disease and it shows that only 2 of the 11 markers originally associated with the phenotype do not depend on assumptions about the missing data mechanism.
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