title: A two-step procedure for constructing confidence intervals of trait loci with application to a rheumatoid arthritis dataset.
abstract: Preliminary genome screens are usually succeeded by fine mapping analyses focusing on the regions that signal linkage. It is advantageous to reduce the size of the regions where follow-up studies are performed, since this will help better tackle, among other things, the multiplicity adjustment issue associated with them. We describe a two-step approach that uses a confidence set inference procedure as a tool for intermediate mapping (between preliminary genome screening and fine mapping) to further localize disease loci. Apart from the usual Hardy-Weiberg and linkage equilibrium assumptions, the only other assumption of the proposed approach is that each region of interest houses at most one of the disease-contributing loci. Through a simulation study with several two-locus disease models, we demonstrate that our method can isolate the position of trait loci with high accuracy. Application of this two-step procedure to the data from the Arthritis Research Campaign National Repository also led to highly encouraging results. The method not only successfully localized a well-characterized trait contributing locus on chromosome 6, but also placed its position to narrower regions when compared to their LOD support interval counterparts based on the same data.
authors.affiliation: Department of Statistics, Ohio State University, Columbus, 43210, USA.
authors.forename: Charalampos
authors.initials: C
authors.lastname: Papachristou
authors.forename: Shili
authors.initials: S
authors.lastname: Lin
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics*; D002874:Chromosome Mapping / Q000379:methods; D002896:Chromosomes, Human, Pair 6; D016001:Confidence Intervals; D006801:Humans; D008126:Lod Score; D008957:Models, Genetic; D040641:Quantitative Trait Loci / Q000235:genetics*