title: Comparison of family-based association tests in chromosome regions selected by linkage-based confidence intervals.
abstract: We use the Genetic Analysis Workshop 14 simulated data to explore the effectiveness of a two-stage strategy for mapping complex disease loci consisting of an initial genome scan with confidence interval construction for gene location, followed by fine mapping with family-based tests of association on a dense set of single-nucleotide polymorphisms. We considered four types of intervals: the 1-LOD interval, a basic percentile bootstrap confidence interval based on the position of the maximum Zlr score, and asymptotic and bootstrap confidence intervals based on a generalized estimating equations method. For fine mapping we considered two family-based tests of association: a test based on a likelihood ratio statistic and a transmission-disequilibrium-type test implemented in the software FBAT. In two of the simulation replicates, we found that the bootstrap confidence intervals based on the peak Zlr and the 1-LOD support interval always contained the true disease loci and that the likelihood ratio test provided further strong confirmatory evidence of the presence of disease loci in these regions.
authors.affiliation: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario, Canada. lewinger@usc.edu
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Lewinger
authors.forename: Sophia S F
authors.initials: SS
authors.lastname: Lee
authors.forename: Joanna
authors.initials: J
authors.lastname: Biernacka
authors.forename: Long Yang
authors.initials: LY
authors.lastname: Wu
authors.forename: Haijiang Steven
authors.initials: HS
authors.lastname: Shi
authors.forename: Shelley B
authors.initials: SB
authors.lastname: Bull
mesh_terms: D002877:Chromosomes, Human / Q000235:genetics*; D016001:Confidence Intervals; D004194:Disease / Q000235:genetics; D005190:Family; D008040:Genetic Linkage; D055106:Genome-Wide Association Study; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics; D020161:Physical Chromosome Mapping; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015203:Reproducibility of Results