Significance testing in association studies.

The null distribution is the standard normal distribution and the expected distribution of the association statistics under the assumption that the effect size is 0. Each variant’s association statistic in Eq 2 is computed, and its significance is evaluated using the null distribution. If the statistic falls in the significance region of the distribution, the variant is declared associated. In this example, S1 is not significant, whereas S2 and S3 are significant. The exact location of the threshold is defined as the location on the x-axis where the tail probability area equals the significance threshold (S). This is denoted using the quantile of the standard normal .