Genome-first determination of the prevalence and penetrance of eight germline myeloid malignancy predisposition genes: a study of two population-based cohorts.

• Tác giả: David J Carey, Jeremy S Haley, Rachel M Hendricks, Jung Kim, Lisa J McReynolds, Uyenlinh L Mirshahi, Mark Louie Ramos, Douglas R Stewart
• Ngôn ngữ: eng
• Thông tin xuất bản: England : Leukemia , 2025
• Bộ sưu tập: NCBI
• ID: 720194

Tóm tắt

 It is estimated that 10% of individuals with a myeloid malignancy carry a germline susceptibility. Using the genome-first approach, in which individuals were ascertained on genotype alone, rather than clinical phenotype, we quantified the prevalence and penetrance of pathogenic germline variants in eight myeloid malignancy predisposition (gMMP) genes. ANKRD26, CEBPA, DDX41, MECOM, SRP72, ETV6, RUNX1 and GATA2, were analyzed from the Geisinger MyCode DiscovEHR (n = 170,503) and the United Kingdom Biobank (UKBB, n = 469,595). We identified a high risk of myeloid malignancies (MM) (odds ratio[OR] all genes: DiscovEHR, 4.6 [95% confidential interval (CI) 2.1-9.7], p <
  0.0001
  UKBB, 6.0 [95% CI 4.3-8.2], p = 3.1 × 10