As in the simulation study, MR2 shows some difficulties in teasing out complex relationships within the responses, which are mostly directed, e.g., MDD → BD, or mediated, e.g., ADH → MDD → AN, and detected by MR2 as MDD-BD and ADHD-AN, once the causal effects have been detected, and vice versa. The gene discussed is AVP; the disease is major depressive disorder.