Rare variant association methods exhibit higher than expected rates of spurious associations.

<p>Each square represents a confounding scenario set by different values of disease risks, parameterized by <i>Y</i>, and the proportions of each sampled subpopulation, parameterized by <i>X</i> as presented in the text. A value of 0.0 for <i>X</i> indicates an equal proportion of each subpopulation in the study pool and 0.00 for <i>Y</i> indicates an equal disease risk. Spurious association rates (SAR) lower than 5% are represented as white, with other levels signified by sequential coloration with red the lowest and blue the highest. Actual values of the SAR can be found in Figure S2 in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0065834#pone.0065834.s001" target="_blank">File S1</a>.