Nonparametric linkage and family-based association studies of a simulated complex disorder

Affected sibling pairs are widely used to identify chromosomal regions harboring genetic loci underlying common disease. We explore the utility of nonparametric sibling pair and family-based association methods to search for disease susceptibility loci in simulated pedigree data for a qualitative disease trait. Logistic regression was used to model gene x gene and gene x environment interactions when significant linkage and association were detected. Using these methods, we were able to detect three of the four susceptibility loci underlying the disease trait with multipoint lod scores of 1.0 or greater.