Rare penetrant mutations confer severe risk of common diseases.
Science
; 380(6648): eabo1131, 2023 06 02.
Article
en En
| MEDLINE
| ID: mdl-37262146
ABSTRACT
We examined 454,712 exomes for genes associated with a wide spectrum of complex traits and common diseases and observed that rare, penetrant mutations in genes implicated by genome-wide association studies confer ~10-fold larger effects than common variants in the same genes. Consequently, an individual at the phenotypic extreme and at the greatest risk for severe, early-onset disease is better identified by a few rare penetrant variants than by the collective action of many common variants with weak effects. By combining rare variants across phenotype-associated genes into a unified genetic risk model, we demonstrate superior portability across diverse global populations compared with common-variant polygenic risk scores, greatly improving the clinical utility of genetic-based risk prediction.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Penetrancia
/
Predisposición Genética a la Enfermedad
/
Herencia Multifactorial
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Science
Año:
2023
Tipo del documento:
Article
País de afiliación:
Estados Unidos