Sample sizes from the 103 cG×E studies are depicted in Figure 2B. The median sample size, shown as a vertical line in Figure 2A, was 345. Assuming a moderate effect size of r2=0.001, statistical power was less than 10% for the median sample size. Given large and very large effect sizes, cG×E studies required sample sizes of ~600 and ~50 to reach sufficient statistical power (80%) to reject the null. In sum, unless cG×E effect sizes are over an order of magnitude larger than the typical genetic main effect sizes detected in GWA studies, then cG×E studies have generally been underpowered, perhaps severely so, a conclusion also reached by others (23, 32).
