Abstract
BACKGROUND: Opioid use disorder (OUD) has become an urgent health problem. People with OUD often experience comorbid medical conditions. Systematical approaches to identifying co-occurring conditions of OUD can facilitate a deeper understanding of OUD mechanisms and drug discovery. This study presents an integrated approach combining data mining, network construction and ranking, and hypothesis-driven case-control studies using patient electronic health records (EHRs). METHODS: First, we mined comorbidities from the US Food and Drug Administration Adverse Event Reporting System (FAERS) of 12 million unique case reports using frequent pattern-growth algorithm. The performance of OUD comorbidity mining was measured by precision and recall using manually curated known OUD comorbidities. We then constructed a disease comorbidity network using mined association rules and further prioritized OUD comorbidities. Last, novel OUD comorbidities were independently tested using EHRs of 75 million unique patients. RESULTS: The OUD comorbidities from association rules mining achieves a precision of 38.7% and a recall of 78.2 Based on the mined rules, the global DCN was constructed with 1916 nodes and 32,175 edges. The network-based OUD ranking result shows that 43 of 55 known OUD comorbidities were in the first decile with a precision of 78.2%. Hypothyroidism and type 2 diabetes were two top-ranked novel OUD comorbidities identified by data mining and network ranking algorithms. Based on EHR-based case-control studies, we showed that patients with OUD had significantly increased risk for hyperthyroidism (AOR = 1.46, 95% CI 1.43-1.49, p value < 0.001), hypothyroidism (AOR = 1.45, 95% CI 1.42-1.48, p value < 0.001), type 2-diabetes (AOR = 1.28, 95% CI 1.26-1.29, p value < 0.001), compared with individuals without OUD. CONCLUSION: Our study developed an integrated approach for identifying and validating novel OUD comorbidities from health records of 87 million unique patients (12 million for discovery and 75 million for validation), which can offer new opportunities for OUD mechanism understanding, drug discovery, and multi-component service delivery for co-occurring medical conditions among patients with OUD.