Phenome‐Wide Association Studies Uncover a Novel Association of Increased Atrial Fibrillation in Male Patients With Systemic Lupus Erythematosus

Objective Phenome‐wide association studies (Phe WAS ) scan across billing codes in the electronic health record ( EHR ) and re‐purpose clinical EHR data for research. In this study, we examined whether Phe WAS could function as an EHR‐based discovery tool for systemic lupus erythematosus ( SLE ) and identified novel clinical associations in male versus female patients with SLE . Methods We used a de‐identified version of the Vanderbilt University Medical Center EHR , which includes more than 2.8 million subjects. We performed EHR ‐based Phe WAS to compare SLE patients with age‐, sex‐, and race‐matched control subjects and to compare male SLE patients with female SLE patients, controlling for multiple testing using a false discovery rate ( FDR ) P value of 0.05. Results We identified 1,097 patients with SLE and 5,735 matched control subjects. In a comparison of patients with SLE and matched controls, SLE patients were shown to be more likely to have International Classification of Diseases, Ninth Revision codes related to the SLE disease criteria. In the Phe WAS of male versus female SLE patients, with adjustment for age and race, male patients were shown to be more likely to have atrial fibrillation (odds ratio 4.50, false discovery rate P = 3.23 × 10 −3 ). Chart review confirmed atrial fibrillation, with the majority of patients developing atrial fibrillation after the SLE diagnosis and having multiple risk factors for atrial fibrillation. After adjustment for age, sex, race, and coronary artery disease, SLE disease status was shown to be significantly associated with atrial fibrillation ( P = 0.002). Conclusion Using Phe WAS to compare male and female patients with SLE , we identified a novel association of an increased incidence of atrial fibrillation in male patients. SLE disease status was shown to be independently associated with atrial fibrillation, even after adjustment for age, sex, race, and coronary artery disease. These results demonstrate the utility of Phe WAS as an EHR‐based discovery tool for SLE .