Interval estimation of disease loci: development and applications of new linkage methods

Three variants of the confidence set inference (CSI) procedure were proposed and applied to both the simulated and the Collaborative Study on the Genetics of Alcoholism (COGA) data. For each of the two applications, we first performed a preliminary genome scan study based on the microsatellite markers using the GENEHUNTER+ software to identify regions that potentially harbor disease loci. For each such region, we estimated the sibling identity-by-descent sharing probability distribution at the putative disease locus. Based on these estimated probabilities, the CSI procedures were employed to further localize the disease loci using the single-nucleotide polymorphism markers, leading to confidence intervals/regions for their locations. For our analysis with the simulated data, we had knowledge of the simulating models at the time we performed the analysis.