Exome Sequencing Enhances Screening for Familial Hypercholesterolemia Within a Multi-Site Healthcare System

作者：N. Jewel Samadder, Mariah Schroeder, Molly M. Voss, Fadi Shamoun, Iftikhar J. Kullo, Timothy B. Curry, Elisa J. F. Houwink, Michelle L. Bublitz, Lorelei A. Bandel, Sebastian M. Armasu, Robert A. Vierkant, Matthew J. Ferber, Rory J. Olson, Jennifer Tan-Arroyo, Joel A. Morales‐Rosado, Eric W. Klee, Nicholas B. Larson, Teresa Kruisselbrink, Jan B. Egan, Jennifer L. Kemppainen, Jessa Bidwell, Jennifer L. Anderson, Tammy M. McAllister, Linnea M. Baudhuin, Katie L. Kunze, Michael A. Golafshar, R. John Presutti, Jolene M. Summer-Bolster, Konstantinos N. Lazaridis · 发表于：Circulation Genomic and Precision Medicine · 年份：2025 · DOI：10.1161/circgen.125.005174 · 被引用次数：3 · 研究领域：Lipoproteins and Cardiovascular Health、Genomics and Rare Diseases、Genetic Associations and Epidemiology

BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder that increases risk for premature coronary artery disease and has accessible and effective interventions. The Dutch lipid clinic network is currently the most used diagnostic criterion; however, genetic sequencing provides a definitive diagnosis of FH. The goals of this study were to determine whether germline genetic screening using exome sequencing could be used to efficiently identify individuals who were genotype positive for FH. METHODS: Participants were recruited from 3 geographically and racially diverse sites in the United States (Rochester, MN; Phoenix, AZ; and Jacksonville, FL). Participants underwent Exome+ sequencing (dba Helix, San Mateo, CA) and return of results for specific genetic findings in APOB , LDLR , or PCSK9 . A chart review was performed to collect demographics, personal, and family cardiovascular history. RESULTS: At the time of the study, 84 413 participants were enrolled in the Tapestry study. Annotation and interpretation of all variants in genes for FH resulted in the identification of 419 likely pathogenic and pathogenic variants (prevalence, 0.50%), which included 116 APOB , 298 LDLR , and 5 PCSK9 . Sixty-six percent were female, the mean body mass index was 27.3, with 12.3% reporting a history of diabetes. Hypertriglyceridemia (≥150 mg/dL) was present in 39.5% and reduced HDL (<50 mg/dL) was present in 56.7% of patients. 27.5% of patients were not on c...