Reliability of these conclusions is based on the following the three pillar criteria: (a) statistically significant association between depression and outcome (HOMA-IR); (b) exposure (BDI-II score) must have an effect on the mediator (PCSK9), (c) the mediator has to be associated with the outcome (HOMA-IR) when exposure is controlled, i.e., after adjusting for PCSK9 levels. The gene discussed is PCSK9; the disease is depressive symptom measurement.