OD and CD TD analyses were performed separately and without considering an individual’s exposure or dependence status for the other drug. Analyses were stratified by genotyping platform and genetically determined ancestry and combined with inverse variance weighted meta-analysis. Variants with P-values < 1.0 × 10−5 were tested in the replication samples. Association tests were performed using Cox proportional hazards regression [40] implemented in the R package Survival (https://cran.r-project.org/web/views/Survival.html). Cases had a lifetime DSM-IV OD or CD diagnosis and controls did not, although they could have endorsed two or fewer of the dependence criteria. All controls were exposed to cocaine or opioids (at least one reported use, including prescription) in their respective analyses. Imputed allele dosage was the predictor variable and models were adjusted for age (in COGA and CATS only, ten-year-age cohorts in COGA), sex, and the first five PCs (calculated within each ancestry group). The cluster option was used to account for the presence of related individuals in the samples by generating robust variance estimates. OD and CD TD analyses were performed separately and without considering an individual’s status
