Understanding the biology of human responses to opioids may lead to effective preventive strategies and treatments to reduce OD and its harmful consequences. Human genetic research has the potential to dissect the basis of inter-individual variability in the response to opioid exposure (i.e., whether an individual develops dependence on opioids). Genome-wide association studies (GWAS) of large cohorts have identified a number of risk loci and molecular pathways involved in the predisposition to numerous psychiatric disorders and behavioral traits5, 6. Previous OD GWAS included up to 10,000 participants and identified genome-wide significant (GWS) associations in KCNG2, KCNC1, APBB2, CNIH3, and RGMA7–10. However, there was no consistency across the previous OD GWAS with respect to the individual GWS loci, probably due to the limited statistical power and differences in case and control definitions in the context of polygenic architecture (thousands of causal loci with small effect).
