The two heavy opioid user clusters, Groups 4 and 5, were the largest among the four opioid user groups and had the highest estimated heritability: 0.69 (SE=0.06) and 0.76 (SE=0.05), respectively (p’s<10−30). The heritability of the other two user groups, Groups 2 and 3, was also relatively high: 0.49 (SE = 0.07) and 0.53 (SE=0.06), respectively (p’s<10−12). The non-opioid user Group 1 showed a heritability of 0.62 (SE=0.06, p<10−18). Race was a highly significant covariate in all groups (p’s ranging from <10−43 to 10−84), sex was a significant covariate in all groups except Group 2 (p’s ranging from <10−6 to 10−19), and age was a significant covariate in Groups 1, 3 and 5 (p’s ranging from <10−6 to 10−7). Our sensitivity analysis on heritability estimation using different combinations of covariates (Supplementary Table 3) showed that the inclusion of race as a covariate reduced the estimated heritability by about 0.1 for all groups.
