Clinical care site data integration reveals heterogeneity in EHR phenotyping and healthcare utilization patterns

Objective: Genomic research using electronic health record (EHR)-linked biobanks is influenced by heterogeneity in the clinical settings (care sites) where encounters occur. We developed two methods leveraging care site data: ClinicScan identifies where phenotype documentation occurs, and ClinicWAS identifies specialty utilization patterns associated with a risk factor. Materials and Methods: We extracted care sites for each clinical encounter at an academic medical center and mapped each to a clinical specialty. ClinicScan summarizes the specialty distribution of a user-specified diagnosis; ClinicWAS fits a logistic regression for each care site to identify specialty encounters associated with a user-specified risk factor. We applied ClinicScan to depression to test whether requiring a psychiatry encounter strengthened the association between a polygenic risk score (PRS) and a depression phenotype, and ClinicWAS to a coronary heart disease (CHD) PRS to identify sites enriched for high-risk patients. Results: Across 64,983,257 encounters, 2,544 care sites mapped to 57 specialties. Most depression diagnoses occurred in primary care (30.3%) and psychiatry (19.8%). Requiring a psychiatry encounter strengthened the PRS-phenotype association (OR=1.30, 95% CI 1.26-1.35) versus two or more diagnosis codes alone (OR=1.21, 95% CI 1.19-1.24). CHD ClinicWAS identified 19 associated care sites, including 5 catheterization labs. Men and women with high genetic risk (PRS[≥]95th percentile) underwent catheterization for CHD 3.1 (1.5-4.6) and 4.6 (2.5-6.7) years earlier than normal-risk participants, respectively. Discussion: Care site data capture phenotype heterogeneity that otherwise distorts EHR-based phenotypes and obscures high-risk subpopulations. Conclusion: Clinical care site data are an under-utilized resource in EHR-linked biobanks.