A genome-first approach to characterize DICER1 pathogenic variant prevalence, penetrance and cancer, thyroid, and other phenotypes in 2 population-scale cohorts.

ABSTRACT:

Purpose

Population-scale, exome-sequenced cohorts with linked electronic health records (EHR) permit genome-first exploration of phenotype. Phenotype and cancer risk are well-characterized in children with a pathogenic DICER1 (HGNC ID:17098) variant. Here, the prevalence, penetrance and phenotype of pathogenic germline DICER1 variants in adults was investigated in two population-scale cohorts.

Methods

Variant pathogenicity was classified using published DICER1 ClinGen criteria in the UK Biobank (469,787 exomes; unrelated: 437,663) and Geisinger (170,503 exomes; unrelated: 109,789) cohorts. In the UK Biobank cohort, cancer diagnoses in the EHR, cancer and death registry were queried. For the Geisinger cohort, the Geisinger Cancer Registry and EHR were que

SUBMITTER: Kim J 

PROVIDER: S-EPMC11271802 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature