Abstract HUP3: Determining genetic contributions in young stroke from TAPESTRY whole exome sequencing data

• DOI: 10.1161/str.56.suppl_1.hup3
• Publication Date: 2025-01-30T10:08:16Z
• Authors: Gyanendra Kumar; Samantha Brown; Konstantinos Laza...; Alexandria Swanson; Jan Egan; Mariah Schroeder; William Libling; Brenna Beezhold; Robert Vierkant; Tony Luehrs; Hugues Sicotte; Charu Kaiwar; Jean-Pierre Kocher
• Keywords: Stroke; Exome; Clinical neurology

Introduction: The lack of understanding about the genetic and molecular basis young stroke (<55 years age) has hindered development diagnostic, management, therapeutic approaches. Whole exome sequencing (WES) can be leveraged as a tool for studying etiological processes underlying stroke. At time study inception, this is single largest WES in unique population to uncover elusive etiologies. Methods: Mayo Clinic TAPESTRY database research program conducting whole 100,000 participants. Of these, 406 participants met criteria (18-54 based on ICD-9 ICD-10 diagnostic codes. Controls were without stroke-related ICD diagnosis. Cases matched age, gender, race 1:4 case-control ratio. Ischemic etiology was classified using TOAST classification. To mechanisms, gene centric approach used identify variants our cohort. A list 66 genes known associated with curated existing databases. Various filtration strategies potentially damaging (graphic 1). Results: There cases (363 ischemic 43 hemorrhagic; 291 female; age at onset 39.8±10.4; 368 White) 3,857 controls. classification yielded 20 patients large artery atherosclerosis, 58 cardioembolic, 10 small vessel disease, 148 other determined (58 patent foramen ovale, 50 dissection, 48 hypercoagulable state, 11 Moyamoya, vasculitis, fibromuscular dysplasia), 165 undetermined Several individuals had multiple competing cerebral hemorrhages, there 6 aneurysmal, arteriovenous malformation, 5 hypertensive, 2 substance abuse, 3 trauma, 21 Across entire cohort, 35,054 found within identified from literature. Filtration across 30 44 (20 cryptogenic other: 12 4 cardioembolic) that absent Conclusion: powerful potential mechanisms population. An improved etiologies would improve diagnostics pave way new preventive approaches, thus improving overall care patients.