A Screening Test for in a Large United States Patient Cohort Identifies Broader Risk of Carbamazepine-Induced Adverse Events.

is strongly associated with life-threatening severe skin hypersensitivity reactions in patients treated with carbamazepine (CBZ) and structurally related medications. FDA-approved labeling recommends screening before CBZ therapy in patients of Asian ancestry. In this study, we aimed to (a) identify a direct method for screening , and (b) evaluate prevalence in a large cohort of United States patients. Candidate genetic markers were identified by mining public data. Association was tested in 28,897 individuals by comparing SNP results with high-resolution HLA typing. Retrospective analysis of de-identified SNP and ethnicity data from 130,460 individuals was performed to evaluate the ethnic distribution of in the United States. 28,897 United States individuals showed 100% concordance between and the minor allele of rs144012689 (100% sensitivity/99.97% specificity). Retrospective analysis of 160 positive individuals (66 with physician-reported ethnicity) notably included 28 Asians (42%), 15 African Americans (22%), 11 Caucasians (17%), 2 Hispanics (3%), and 10 "Other" (15%). Screening United States patients for without ethnicity-based preselection identifies more than twice the number of carriers at risk of CBZ-related adverse events than screening patients of Asian ancestry alone. Risk assessment based on ethnicity assumptions may not identify a large portion of at-risk patients in the ethnically diverse United States population.