Eight disease etiologies used in simulation experiments.

Rare variant = disease caused by multiple rare deleterious variants. Low frequency variant = disease caused by multiple low frequency deleterious variants. Key Region variant = rare deleterious variants are localized to key regions. Common variant = disease caused by a single deleterious common variant. The etiologies Rare+Protect, LowFreq+Protect, KeyRegion+Protect and Common+Protect were identical to the first four except that they include protective variants.1Minor allele frequency of deleterious causal variants,2Selection coefficients of deleterious causal variants,3Effect size of deleterious causal variants,4Selection coefficient of protective causal variants,5Effect size of protective modifier variants,6Required functional role of causal and protective variants, NS = coding non-synonymous, AA = African-American simple bottleneck demographic model [44], EA = European-American exponential growth demographic model [19]).* for protective modifier variants with AF5%, for protective modifier variants with AF5%.