of all other groups was below 0.50. The groups that had an early-onset of OD (i.e., highly comorbid and heavy opioid users) largely overlapped in Group E and Group 5. However, the disagreement of the cluster labels assigned to the subjects in either Group E or Group 5 is over 20%, resulted in different heritability estimates. Groups 3 and 4 in our solution were split into Groups A to E using the LMW approach. A substantial minority (12.1%) of subjects from Group A (Low-level or Non-opioid users) with a lifetime OD diagnosis clustered (appropriately) in the opioid user groups in our analysis. Specifically, 332 (10.6%) individuals that were in Group A by the LMW method and in Groups 4 and 5 of our solution received an OD diagnosis and used opioids daily or almost daily, with the majority (85%) having stayed high for a whole day or more. Thus, it was inappropriate to identify these heavy users as Low-level or Non-opioid users. Further, inclusion of these heavy users in the low-level or non-opioid user group increased its phenotypic variance, thereby reducing its heritability.
