Jinwala Zeal, Davis Christal N, SooHoo Jackson F, Gelernter Joel, Kember Rachel L, Vickers-Smith Rachel, Kranzler Henry R
Mental Illness Research, Education and Clinical Center, Crescenz Veterans Affairs Medical Center, Philadelphia, PA, USA.
Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Res Sq. 2025 Aug 21:rs.3.rs-7330342. doi: 10.21203/rs.3.rs-7330342/v1.
Opioids are commonly prescribed to manage acute postoperative pain. However, individuals vary in their opioid dosing needs, with no validated biomarkers to guide prescribing. We used electronic health records (EHR) data from the Million Veteran Program sample to investigate individual differences in opioid analgesic dosing following knee (n=18,540) or hip (n=9,363) arthroplasty. We extracted data from pharmacy records on inpatient opioid medications to estimate average daily morphine milligram equivalent (MME) dosages and used genome-wide association studies (GWAS) to identify genetic variants associated with daily MME dosage, followed by a cross-ancestry and cross-phenotype meta-analysis. We identified two genome-wide significant loci in the African ancestry knee arthroplasty GWAS and three in the Admixed-American ancestry hip arthroplasty GWAS. Multiple other loci in African, Admixed-American, and European populations were nominally significant. The study provides a framework for the use of EHR data to examine the genetics of opioid dosing in post-operative care.
阿片类药物常用于管理术后急性疼痛。然而，个体对阿片类药物的剂量需求各不相同，且尚无经过验证的生物标志物来指导用药。我们使用了来自百万退伍军人计划样本的电子健康记录（EHR）数据，以研究膝关节置换术（n = 18,540）或髋关节置换术（n = 9,363）后阿片类镇痛药物剂量的个体差异。我们从住院阿片类药物的药房记录中提取数据，以估计平均每日吗啡毫克当量（MME）剂量，并使用全基因组关联研究（GWAS）来识别与每日MME剂量相关的基因变异，随后进行跨祖先和跨表型的荟萃分析。我们在非洲血统膝关节置换术的GWAS中确定了两个全基因组显著位点，在混血美国血统髋关节置换术的GWAS中确定了三个。在非洲、混血美国和欧洲人群中的多个其他位点具有名义上的显著性。该研究为利用EHR数据研究术后护理中阿片类药物剂量的遗传学提供了一个框架。
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