Figure 2  Directed Acyclic Graph Showing Gene-Environment Dependence by Pleiotropy
Notation as in Figure 1. D has pleiotropic effects on X and Y, but there is no direct effect of X on Y. For example, a CYP3A variant (D) affects hormone levels, which independently affect age at menarche (X) and breast cancer (Y). Age at menarche is an independent risk factor for breast cancer because it marks additional causal processes (G).