Fig. 3.

Complex diseases have intrinsically weak genetic effects, as illustrated by a Manhattan plot with only a few significant P-values highlighted in green color. The effect sizes corresponding to P-values in the Manhattan plot look “L-shaped,” reflecting the idea that the majority of signals are just noise with very little effect sizes (e.g., as measured by ${log}^2\left(\mathrm{OR}\right)$ so the bulk of the effect size distribution is around zero and it is increasingly less likely to find a signal with a large effect size