Sequence Kernel Association Tests for the Combined Effect of Rare and Common Variants  Iuliana Ionita-Laza, Seunggeun Lee, Vlad Makarov, Joseph D. Buxbaum, Xihong Lin  The American Journal of Human Genetics  Volume 92, Issue 6, Pages 841-853 (June 2013) DOI: 10.1016/j.ajhg.2013.04.015 Copyright © 2013 The American Society of Human Genetics Terms and Conditions

Figure 1 Power of the Burden-C Test with Different Frequency Thresholds to Separate Rare from Common Variants Power (α = 2.5 × 10−6) of using different frequency thresholds to separate rare and common variants (fixed values 0.005, 0.01, and 0.05 versus 1/2n) for the proposed combination method burden-C for model 1 (in Table S1) and for n = 500, 1,000, 2,000, and 5,000 in a region of size 25 kb. The proportion of associated variants (PC) in the region is 30%. The sample-dependent threshold 1/2n is: 0.03 (n = 500), 0.02 (n = 1,000), 0.015 (n = 2,000), and 0.01 (n = 5,000). The American Journal of Human Genetics 2013 92, 841-853DOI: (10.1016/j.ajhg.2013.04.015) Copyright © 2013 The American Society of Human Genetics Terms and Conditions

Figure 2 Power for Models 1–3 in 25 kb Regions Power (α = 2.5 × 10−6) of the tests in Table 1 for a region of size 25 kb (l = 25 kb) across disease models 1–3 in Table 2 for n = 1,000, 2,000, and 5,000 and two different values for the proportion of associated variants in a region: 10% (i.e., PC = 0.1) or 30% (i.e., PC = 0.3). The American Journal of Human Genetics 2013 92, 841-853DOI: (10.1016/j.ajhg.2013.04.015) Copyright © 2013 The American Society of Human Genetics Terms and Conditions

Figure 3 Power for Models 4–6 in 25 kb Regions Power (α = 2.5 × 10−6) of the tests in Table 1 for a region of size 25 kb (l = 25 kb) across disease models 4–6 in Table 2 for n = 1,000, 2,000, and 5,000 and two different values for the proportion of associated variants in a region: 10% (i.e., PC = 0.1) or 30% (i.e., PC = 0.3). The American Journal of Human Genetics 2013 92, 841-853DOI: (10.1016/j.ajhg.2013.04.015) Copyright © 2013 The American Society of Human Genetics Terms and Conditions

Figure A1 Variance Explained by Rare versus Common Risk-Associated Variants Variance explained by common associated variants versus rare associated variants in a 25 kb region (based on 100 random regions). Ten percent of all variants in the region are associated with the trait. Each dot corresponds to one random 25 kb region. Variance explained by common variants (MAF > 1/2n) is on the y axis, and variance explained by rare variants (MAF < 1/2n) is on the x axis. The American Journal of Human Genetics 2013 92, 841-853DOI: (10.1016/j.ajhg.2013.04.015) Copyright © 2013 The American Society of Human Genetics Terms and Conditions