“…Despite substantial effort to explicate the genetic etiology of opioid use and associated sequalae (Cheng et al, 2020 ; Deak et al, 2022 ; Jensen, 2016 ; Zhou et al, 2020 ), many twin and genomic studies have struggled to identify significant and/or replicable findings (Crist, Reiner, & Berrettini, 2019 ; Polimanti et al, 2020 ; Reed & Kreek, 2021 ). Heritability estimates of opioid use derived from twin studies have been varied, ranging from 0% to 79% (Dash, Martin, Agrawal, Lynskey, & Slutske, 2022 ; Karkowski, Prescott, & Kendler, 2000 ; Kendler, Aggen, Tambs, & Reichborn-Kjennerud, 2006 ; Kendler, Jacobson, Prescott, & Neale, 2003 ; Kendler, Karkowski, Neale, & Prescott, 2000a ; Kendler, Karkowski, & Prescott, 1999 ; Tsuang et al, 1998 ; Van den Bree, Johnson, Neale, & Pickens, 1998 ). Such discrepancies in findings regarding the relative influence of genes and environment on opioid use may be at least partially attributable to the operationalization of opioid use as a single behavior encompassing both prescription opioid misuse (POM) and heroin use: emerging evidence suggests that POM and heroin use may be differentially influenced by genes and environment, such that POM is more strongly influenced by genes and heroin use is more strongly influenced by common environment (Dash et al, 2022 ; Gillespie et al, 2019 ).…”