We performed genome-wide model dependent and independent analyses on a simulated data set of 400 families segregating for a rare disorder. Regions on chromosomes 1, 3, and 5 were consistently indicated across the various analyses performed. Follow-up analyses included stratification for locus heterogeneity and clinical phenotype and studies of gene x gene and gene x environment interaction. The region around D1G024 was most notable, showing strong association and linkage with the trait. We also identified regions D3G043-46 and D5G037-39 by strong linkage and association findings and region D1G001-09 by linkage analysis. A complex statistical interaction was suggested between D1G024, D3G046 and environmental factor 1. This report suggests that traditional methods of analysis can be implemented to analyze and describe the mechanisms that may underlie the more complex genetic disorders.