Quantifying the polygenic contribution to variable expressivity in eleven rare genetic disorders.
Nat Commun
; 10(1): 4897, 2019 10 25.
Article
en En
| MEDLINE
| ID: mdl-31653860
ABSTRACT
Rare genetic disorders (RGDs) often exhibit significant clinical variability among affected individuals, a disease characteristic termed variable expressivity. Recently, the aggregate effect of common variation, quantified as polygenic scores (PGSs), has emerged as an effective tool for predictions of disease risk and trait variation in the general population. Here, we measure the effect of PGSs on 11 RGDs including four sex-chromosome aneuploidies (47,XXX; 47,XXY; 47,XYY; 45,X) that affect height; two copy-number variant (CNV) disorders (16p11.2 deletions and duplications) and a Mendelian disease (melanocortin 4 receptor deficiency (MC4R)) that affect BMI; and two Mendelian diseases affecting cholesterol familial hypercholesterolemia (FH; LDLR and APOB) and familial hypobetalipoproteinemia (FHBL; PCSK9 and APOB). Our results demonstrate that common, polygenic factors of relevant complex traits frequently contribute to variable expressivity of RGDs and that PGSs may be a useful metric for predicting clinical severity in affected individuals and for risk stratification.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Estatura
/
Índice de Masa Corporal
/
Herencia Multifactorial
/
Enfermedades Raras
/
LDL-Colesterol
/
Obesidad
Tipo de estudio:
Prognostic_studies
Límite:
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Nat Commun
Asunto de la revista:
BIOLOGIA
/
CIENCIA
Año:
2019
Tipo del documento:
Article
País de afiliación:
Estados Unidos