An ordered subset approach to including covariates in the transmission disequilibrium test.
Clinical heterogeneity of a disease may reflect an underlying genetic heterogeneity, which may hinder the detection of trait loci. Consequently, many statistical methods have been developed that allow for the detection of linkage and/or association signals in the presence of heterogeneity.This report describes the work of two parallel investigations into similar approaches to ordered subset analysis, based on an observed covariate, in the framework of family-based association analysis using Genetic Analysis Workshop 15 simulated data.With an appropriate choice of covariate, both approaches allow detection of two loci that are undetectable by the classical transmission-disequilibrium test. For a third locus, detectable by the classical transmission-disequilibrium test, a substantial increase of power of detection is shown.
Perdry
Hervé
H
INSERM U535, BP 1000, Villejuif, 94817, France and Université Paris-Sud, IFR69, Villejuif, 94817, France.
Maher
Brion S
BS
Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, PO Box 980126, Richmond, Virginia 23298, USA.|Center for Craniofacial and Dental Genetics, Cellomics Suite 500, 100 Technology Drive, University of Pittsburgh School of Dental Medicine, Pittsburgh, Pennsylvania 15219, USA.
Babron
Marie-Claude
MC
INSERM U535, BP 1000, Villejuif, 94817, France and Université Paris-Sud, IFR69, Villejuif, 94817, France.
McHenry
Toby
T
Center for Craniofacial and Dental Genetics, Cellomics Suite 500, 100 Technology Drive, University of Pittsburgh School of Dental Medicine, Pittsburgh, Pennsylvania 15219, USA.
Clerget-Darpoux
Françoise
F
INSERM U535, BP 1000, Villejuif, 94817, France and Université Paris-Sud, IFR69, Villejuif, 94817, France.
Marazita
Mary L
ML
Center for Craniofacial and Dental Genetics, Cellomics Suite 500, 100 Technology Drive, University of Pittsburgh School of Dental Medicine, Pittsburgh, Pennsylvania 15219, USA.