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BridgePRS leverages shared genetic effects across ancestries to increase polygenic risk score portability.
Hoggart, Clive J; Choi, Shing Wan; García-González, Judit; Souaiaia, Tade; Preuss, Michael; O'Reilly, Paul F.
Afiliación
  • Hoggart CJ; Department of Genetics and Genomic Sciences, Icahn School of Medicine, Mount Sinai, New York, NY, USA. clivehoggart@gmail.com.
  • Choi SW; Department of Genetics and Genomic Sciences, Icahn School of Medicine, Mount Sinai, New York, NY, USA.
  • García-González J; Regeneron Genetics Center, Tarrytown, NY, USA.
  • Souaiaia T; Department of Genetics and Genomic Sciences, Icahn School of Medicine, Mount Sinai, New York, NY, USA.
  • Preuss M; Department of Cellular Biology, Suny Downstate Health Sciences, Brooklyn, NY, USA.
  • O'Reilly PF; The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine, Mount Sinai, New York, NY, USA.
Nat Genet ; 56(1): 180-186, 2024 Jan.
Article en En | MEDLINE | ID: mdl-38123642
ABSTRACT
Here we present BridgePRS, a novel Bayesian polygenic risk score (PRS) method that leverages shared genetic effects across ancestries to increase PRS portability. We evaluate BridgePRS via simulations and real UK Biobank data across 19 traits in individuals of African, South Asian and East Asian ancestry, using both UK Biobank and Biobank Japan genome-wide association study summary statistics; out-of-cohort validation is performed in the Mount Sinai (New York) BioMe biobank. BridgePRS is compared with the leading alternative, PRS-CSx, and two other PRS methods. Simulations suggest that the performance of BridgePRS relative to PRS-CSx increases as uncertainty increases with lower trait heritability, higher polygenicity and greater between-population genetic diversity; and when causal variants are not present in the data. In real data, BridgePRS has a 61% larger average R2 than PRS-CSx in out-of-cohort prediction of African ancestry samples in BioMe (P = 6 × 10-5). BridgePRS is a computationally efficient, user-friendly and powerful approach for PRS analyses in non-European ancestries.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Predisposición Genética a la Enfermedad / Puntuación de Riesgo Genético Límite: Humans Idioma: En Revista: Nat Genet Asunto de la revista: GENETICA MEDICA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Predisposición Genética a la Enfermedad / Puntuación de Riesgo Genético Límite: Humans Idioma: En Revista: Nat Genet Asunto de la revista: GENETICA MEDICA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos