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

Author:

Brummett Chad1,Annis Aubrey2ORCID,Gunaseelan Vidhya2,Smith Albert2ORCID,Abecasis Goncaol3,Larach Daniel4ORCID,Zawistowski Matthew5ORCID,Frangakis Stephan2

Affiliation:

1. Division of Pain Medicine, Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, MI

2. University of Michigan

3. Regeneron Genetics Center

4. Vanderbilt University

5. University of Michigan - Department of Biostatistics

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.

Publisher

Research Square Platform LLC

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3