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Disclaimer: Supplementary materials have been peer-reviewed but not copyedited.

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Supplemental Data Description

Supplemental Data include the MAF distribution of the simulated non-synonymous variants; two Q-Q plots and another set of simulation results under a completely different simulation model. It also includes DHS results for Hispanics.

Fig. S1. Minor allele frequency spectrum of nonsynonymous variants based on the forward-time simulation model.

Fig. S2. Q-Q Plots of 40,000 P-values on the –log10 scale for the σ-P method at PAR = 0 in coding regions of varying lengths.

Fig. S3. Q-Q Plots of 40,000 P-values on the –log10 scale for the σ-MidP method at PAR = 0 in coding regions of varying lengths.

Fig. S4. Minor allele frequency spectrum under the Wright's distribution model.

Fig. S5. In panels (A–C), power comparisons under the additive model with two detrimental variants and zero (panel A), two (panel B), and six (panel C) neutral variants; for panels (D–F), 10 detrimental variants and zero (panel D), 10 (panel E), and 30 (panel F) neutral variants; and for panels G-I, 20 detrimental variants and zero (panel G), 20 (panel H), and 60 (panel I) neutral variants.

Fig. S6. Power comparisons under the additive model with 20 detrimental variants, 20 protective variants, and zero (panel A), five (panel B), 10 (panel C), 20 (panel D) neutral variants generated based on the Wright's distribution as described in the supplementary methods. Sample size is 500 cases and 500 controls.

Fig. S7. In panels (A–C), power comparisons under the dominant model with two detrimental variants and zero (panel A), two (panel B), and six (panel C) neutral variants; for panels (D–F), 10 detrimental variants and zero (panel D), 10 (panel E), and 30 (panel F) neutral variants; and for panels (G–I), 20 detrimental variants and zero (panel G), 20 (panel H), and 60 (panel I) neutral variants.

Fig. S8. Panels (A–D) display power comparisons under the dominant model with 20 detrimental variants, 20 protective variants, and zero (panel A), five (panel B), 10 (panel C), 20 (panel D) neutral variants generated based on the Wright's distribution as described in the supplementary methods.

Table S1 Type I error at 0.05 nominal level when data is generated under the Wright model for varying number of neutral variant sites.

Table S2 Rare-variant association analyses in Hispanics.

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