Comparison of family-based association tests in chromosome regions selected by linkage-based confidence intervals.
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.
Lewinger
Juan Pablo
JP
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario, Canada. lewinger@usc.edu
Lee
Sophia S F
SS
Biernacka
Joanna
J
Wu
Long Yang
LY
Shi
Haijiang Steven
HS
Bull
Shelley B
SB
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