Our interpretive tests examined the robustness of the general substance dependence results and compared them to substance-specific effects. Specifically, to assess the influence of each individual dataset, each of the 20 contributing datasets was, in turn, left out of the meta-analysis. In this leave-one-out test, observing consistency of summary odds ratios would suggest that it is unlikely that the overall meta-analysis result is primarily due to a single study. Also, we meta-analyzed only studies that had assessed all five substances to examine consistency of results; the general dependence controls in these studies were assessed for all five substances and thus more homogenous. Finally, to compare the effect of rs1799971 on general substance dependence liability with its effect on the constituent substance-specific diagnoses, we tested for association using individuals dependent on each specific substance as cases compared to the same controls used in the general dependence analysis (non-dependent on all assessed substances).
