Hunting genetic diseases: Exploring a multistage approach to identifying disease loci

Genomic screen data for a hypothetical disease was used in a two-stage anal ysis to search for disease loci. We performed both trait-model-dependent an d trait-model-free analyses to test their relative power. Results of our fi rst-stage screen in 200 families suggested 13 regions for further analysis. Second-stage follow-up in another 200 families confirmed a single region o n chromosome 3 near marker D3G045 with a combined lod score across all 400 families of 6.24 and a sib-pair maximum lod score (MLS) of 4.79. The MLS we re highly correlated with both the autosomal dominant and autosomal recessi ve lod scores in all data sets, suggesting that both trait-model-dependent and trait-model-free methods can be useful for identifying candidate region s for complex disease loci. Reanalysis of the data using alternative sampli ng schemes suggested that sampling variation has a significant effect on lo cus detection. ((C)) 1999 Wiley-Liss, Inc.