Inclusion of Gene-Gene and Gene-Environment Interactions Unlikely to Dramatically Improve Risk Prediction for Complex Diseases Hugues Aschard, Jinbo.

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Inclusion of Gene-Gene and Gene-Environment Interactions Unlikely to Dramatically Improve Risk Prediction for Complex Diseases Hugues Aschard, Jinbo Chen, Marilyn C. Cornelis, Lori B. Chibnik, Elizabeth W. Karlson, Peter Kraft The American Journal of Human Genetics Volume 90, Issue 6, Pages 962-972 (June 2012) DOI: 10.1016/j.ajhg.2012.04.017 Copyright © 2012 The American Society of Human Genetics Terms and Conditions

Figure 1 Absolute Increase in AUC and cNRI by the Number of Interactions Simulated Breast cancer (BRCA), rheumatoid arthritis (RA), and type 2 diabetes (T2D). The American Journal of Human Genetics 2012 90, 962-972DOI: (10.1016/j.ajhg.2012.04.017) Copyright © 2012 The American Society of Human Genetics Terms and Conditions

Figure 2 Absolute Increase in AUC and cNRI by the Maximum Interaction Effect Simulated Breast cancer (BRCA), rheumatoid arthritis (RA), and type 2 diabetes (T2D). The American Journal of Human Genetics 2012 90, 962-972DOI: (10.1016/j.ajhg.2012.04.017) Copyright © 2012 The American Society of Human Genetics Terms and Conditions

Figure 3 Comparison of Increase in AUC between Models that Include a Low Number of Strong-Interaction Effects with Models that Include a Large Number of Low-Interaction Effects We compared the absolute increase in AUC between models that include two strong interactions (dashed line) and models that include ten low interactions (solid line) for BRCA (blue), RA (green), and T2D (red). Probability density functions were estimated from 1,000 simulations for each scenario. The American Journal of Human Genetics 2012 90, 962-972DOI: (10.1016/j.ajhg.2012.04.017) Copyright © 2012 The American Society of Human Genetics Terms and Conditions

Figure 4 Absolute Increase in Sensitivity by Maximum Interaction Effect and Specify Threshold Breast cancer (BRCA), rheumatoid arthritis (RA), and type 2 diabetes (T2D). The American Journal of Human Genetics 2012 90, 962-972DOI: (10.1016/j.ajhg.2012.04.017) Copyright © 2012 The American Society of Human Genetics Terms and Conditions