Since the Plains Indians derive from one large pedigree we confirmed the significant p values for associations by performing 10,000 simulations using SIMPED (Leal et al, 2005). With this program genotypes can be generated conditional on user-specified frequencies and using the gene-drop method within pedigrees of virtually any size and complexity. Since most of the significant SNPs were in allelic identity, association analysis (t-test between the two homozygous genotypes) was computed for the simulated SNP rs12511372 and a null distribution for the t statistic was generated. This was subsequently used to determine the empirical p value (0.0004) which was close to the p value assuming independence (0.0003). Therefore we were able to undertake analyses that assume independence of individuals.
