Improving polygenic risk prediction in admixed populations by explicitly modeling ancestral-differential effects via GAUDI.
Nat Commun
; 15(1): 1016, 2024 Feb 03.
Article
em En
| MEDLINE
| ID: mdl-38310129
ABSTRACT
Polygenic risk scores (PRS) have shown successes in clinics, but most PRS methods focus only on participants with distinct primary continental ancestry without accommodating recently-admixed individuals with mosaic continental ancestry backgrounds for different segments of their genomes. Here, we develop GAUDI, a novel penalized-regression-based method specifically designed for admixed individuals. GAUDI explicitly models ancestry-differential effects while borrowing information across segments with shared ancestry in admixed genomes. We demonstrate marked advantages of GAUDI over other methods through comprehensive simulation and real data analyses for traits with associated variants exhibiting ancestral-differential effects. Leveraging data from the Women's Health Initiative study, we show that GAUDI improves PRS prediction of white blood cell count and C-reactive protein in African Americans by > 64% compared to alternative methods, and even outperforms PRS-CSx with large European GWAS for some scenarios. We believe GAUDI will be a valuable tool to mitigate disparities in PRS performance in admixed individuals.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Negro ou Afro-Americano
/
Software
/
Estratificação de Risco Genético
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Nat Commun
Assunto da revista:
BIOLOGIA
/
CIENCIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos