Genetic associations of persistent opioid use after surgery: a hypothesis-driven analysis of high-value genetic variants in the Michigan Genomics Initiative dataset

Abstract

Abstract Persistent opioid use after surgery is a common morbidity outcome associated with subsequent opioid use disorder, overdose, and death. While phenotypic associations are known, genetic associations remain unidentified. Here, we conducted the largest genetic study of persistent opioid use after surgery: a candidate analysis among non-Hispanic, European-ancestry Michigan Genomics Initiative participants (3,198 cases and 36,321 surgically exposed controls; 794 cases and 32,656 controls in an “opioid-naive” subanalysis) of high-value genetic variants from 72 opioid-related studies. Associations (p < 0.05) occurred at 14 of 77 variants spanning 23 genes. Two highly referenced genes, OPRD1 and DRD2/ANKK1, had no signals. Eleven occurred in OPRM1 (most significant: rs79704991-T, OR = 1.17, p = 8.7×10− 5). Other associations were rs10886472-GRK5 (p = 0.028), rs4633-COMT (p = 0.017), and rs4680-COMT (p = 0.016). Associations at previously identified OPRM1 variants suggest common biology between persistent opioid use and opioid use disorder, establishing a genetically informed component for the recently described concept of preaddiction patients who receive opioid prescriptions. Lack of significant associations at other variants challenges previous studies’ reliability.