Theoretical and empirical quantification of the accuracy of polygenic scores in ancestry divergent populations.
Nat Commun
; 11(1): 3865, 2020 07 31.
Article
em En
| MEDLINE
| ID: mdl-32737319
ABSTRACT
Polygenic scores (PGS) have been widely used to predict disease risk using variants identified from genome-wide association studies (GWAS). To date, most GWAS have been conducted in populations of European ancestry, which limits the use of GWAS-derived PGS in non-European ancestry populations. Here, we derive a theoretical model of the relative accuracy (RA) of PGS across ancestries. We show through extensive simulations that the RA of PGS based on genome-wide significant SNPs can be predicted accurately from modelling linkage disequilibrium (LD), minor allele frequencies (MAF), cross-population correlations of causal SNP effects and heritability. We find that LD and MAF differences between ancestries can explain between 70 and 80% of the loss of RA of European-based PGS in African ancestry for traits like body mass index and type 2 diabetes. Our results suggest that causal variants underlying common genetic variation identified in European ancestry GWAS are mostly shared across continents.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Asma
/
Herança Multifatorial
/
Polimorfismo de Nucleotídeo Único
/
Diabetes Mellitus Tipo 2
/
Hipertensão
/
Modelos Genéticos
Tipo de estudo:
Diagnostic_studies
/
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
País/Região como assunto:
Africa
/
Asia
/
Europa
Idioma:
En
Revista:
Nat Commun
Assunto da revista:
BIOLOGIA
/
CIENCIA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Austrália