Substance Use Disorders EHR Phenotypes

The derivation and validation of phenotyping definitions to characterize multiple opioid use and misuse phenotypes, and the performance of GWAS using these phentoypes. Assessment of genetic comorbidities with other psychiatric and medical conditions. The Opioid Use Disorder workgroup aims to study the genetics of opioid use disorders (OUD) using electronic health record data across multiple sites from the psycheMERGE network (Vanderbilt, Geisenger, Michigan, Partners, Penn Medicine, Million Veterans Program). We wish to accomplish the following aims: 1) derive and validate phenotyping definitions to characterize multiple opioid use and misuse phenotypes, expanding on existing algorithms of OUD (e.g. new persistent use, opioid use escalation, OUD diagnosis, as well as deeply characterizing opioid-exposed controls) and computing novel ones, including unsupervised clustering algorithms to identify OUD sub-types; 2) perform large genome-wide association studies of the phenotypes derived in aim 1 using state-of-the-art multivariate methods including Genomic Structural Equation Modeling, 3) assess genetic comorbidities with other psychiatric and medical conditions via phenome-wide association analyses. Although our analyses will focus on European subjects to boost power for gene discovery, we aim to expand our analyses to non-European populations. This project will result in the largest genetic study of OUD to date, and the phenotyping strategies have the potential to be translated into clinical care.