Demographic history mediates the effect of stratification on polygenic scores.
Elife
; 92020 11 17.
Article
en En
| MEDLINE
| ID: mdl-33200985
ABSTRACT
Population stratification continues to bias the results of genome-wide association studies (GWAS). When these results are used to construct polygenic scores, even subtle biases can cumulatively lead to large errors. To study the effect of residual stratification, we simulated GWAS under realistic models of demographic history. We show that when population structure is recent, it cannot be corrected using principal components of common variants because they are uninformative about recent history. Consequently, polygenic scores are biased in that they recapitulate environmental structure. Principal components calculated from rare variants or identity-by-descent segments can correct this stratification for some types of environmental effects. While family-based studies are immune to stratification, the hybrid approach of ascertaining variants in GWAS but reestimating effect sizes in siblings reduces but does not eliminate stratification. We show that the effect of population stratification depends not only on allele frequencies and environmental structure but also on demographic history.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Sesgo
/
Herencia Multifactorial
/
Estudio de Asociación del Genoma Completo
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Elife
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos