The simulation studies were performed based on three relationship scenarios. (1) In Scenario I, the case group consisted of 250 individuals from 50 pedigrees as seen in Figure 1 with each pedigree having five cases. The entire pedigree information was assumed known for the case group. The control group simply included 250 independent and unrelated individuals. (2) Scenario II was the same as Scenario I except the cases were chosen from a large pedigree of 13 generations and 4070 individuals to simulate the background correlation among individuals. Each set of parents in the 13 generations had one or two offspring, and 1124 individuals were unrelated founders. We assumed that the genealogy of only the last two generations was available. (3) In Scenario III, samples were simulated for 500 related and 500 independent unrelated people. The related individuals were in the final generations of a large pedigree of 13 generations as in Scenario II, but the pedigree information was assumed known for the last three generations. Controls in each of these three scenarios were unrelated, which is the most ideal situation.
