title: Linkage analysis of GAW14 simulated data: comparison of multimarker, multipoint, and conditional approaches.
abstract: The purposes of this study were 1) to examine the performance of a new multimarker regression approach for model-free linkage analysis in comparison to a conventional multipoint approach, and 2) to determine the whether a conditioning strategy would improve the performance of the conventional multipoint method when applied to data from two interacting loci. Linkage analysis of the Kofendrerd Personality Disorder phenotype to chromosomes 1 and 3 was performed in three populations for all 100 replicates of the Genetic Analysis Workshop 14 simulated data. Three approaches were used: a conventional multipoint analysis using the Zlr statistic as calculated in the program ALLEGRO; a conditioning approach in which the per-family contribution on one chromosome was weighted according to evidence for linkage on the other chromosome; and a novel multimarker regression approach. The multipoint and multimarker approaches were generally successful in localizing known susceptibility loci on chromosomes 1 and 3, and were found to give broadly similar results. No advantage was found with the per-family conditioning approach. The effect on power and type I error of different choices of weighting scheme (to account for different numbers of affected siblings) in the multimarker approach was examined.
authors.affiliation: Department of Medical Genetics, University of Cambridge, Cambridge Institute for Medical Research (CIMR), Wellcome Trust/MRC Building, Addenbrooke's Hospital, Cambridge, CB2 2XY, UK. mathew.barber@cimr.cam.ac.uk
authors.forename: Mathew J
authors.initials: MJ
authors.lastname: Barber
authors.forename: Eleanor
authors.initials: E
authors.lastname: Wheeler
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Cordell
mesh_terms: D002874:Chromosome Mapping; D003198:Computer Simulation; D003226:Congresses as Topic; D030541:Databases, Genetic; D005819:Genetic Markers; D005828:Genetics, Population; D006801:Humans; D008957:Models, Genetic; D012044:Regression Analysis; D015203:Reproducibility of Results
chemical_list: D005819:Genetic Markers