No Gene Is an Island: The Flip-Flop Phenomenon Ping-I Lin, Jeffery M. Vance, Margaret A. Pericak-Vance, Eden R. Martin  The American Journal of Human Genetics  Volume 80, Issue 3, Pages 531-538 (March 2007) DOI: 10.1086/512133 Copyright © 2007 The American Society of Human Genetics Terms and Conditions

Figure 1 Penetrance values for each two-locus genotype combination under different models of multilocus effect. The penetrance values were calculated by specifying α=.001, θ1=0.1, and θ2=0.2 for each model. The American Journal of Human Genetics 2007 80, 531-538DOI: (10.1086/512133) Copyright © 2007 The American Society of Human Genetics Terms and Conditions

Figure 2 ORs corresponding to the effect size of allele A under models I and IV. Parameters for each situation are specified. A, f=0.001, θ1=0.1, and θ2=0.2 under model I. B, f=0.001, θ1=0.1, and θ2=−0.2 under model I. C, f=0.001, θ1=0.1, and θ2=0.2 under model IV. D, f=0.001, θ1=0.1, and θ2=−0.2 under model IV. The American Journal of Human Genetics 2007 80, 531-538DOI: (10.1086/512133) Copyright © 2007 The American Society of Human Genetics Terms and Conditions

Figure 3 Directions of allelic association for the A allele in different situations. We used the statisticχ=(PA−PB)/P(1−P)/N, where P=(PA+PB)/2, to demonstrate how the direction of allelic association varies depending on θ2, given the same frequency of the A (and B) allele (∼50%) and model of multilocus effect. θ1 is fixed at 0.1 for all models. Panel A indicates the situation where A is a risk allele and B is also a risk allele; panel B indicates the situation where the A allele is a risk allele and the B allele is a protective allele. The American Journal of Human Genetics 2007 80, 531-538DOI: (10.1086/512133) Copyright © 2007 The American Society of Human Genetics Terms and Conditions

Figure 4 The effect of the Val allele (i.e., the A allele at NlaIII RSP) on SCZD across 32 populations. Allelic effect is presented by OR. For model A, θ1=0.1 and θ2=0.2; for model B, θ1=0.1 and θ2=0.4; for model C, θ1=0.1 and θ2=0.8. For all four models, f=0.001. The American Journal of Human Genetics 2007 80, 531-538DOI: (10.1086/512133) Copyright © 2007 The American Society of Human Genetics Terms and Conditions

Figure 5 The effect of the Val allele (presented by OR) on SCZD in the Cambodian population, given different disease models (i.e., different effect ratios for the P2 promoter compared with the Val allele). The American Journal of Human Genetics 2007 80, 531-538DOI: (10.1086/512133) Copyright © 2007 The American Society of Human Genetics Terms and Conditions