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Leveraging fine-mapping and multipopulation training data to improve cross-population polygenic risk scores
by
Kanai, Masahiro
, Peyrot, Wouter J.
, Weissbrod, Omer
, Martin, Alicia R.
, Okada, Yukinori
, Finucane, Hilary K.
, Price, Alkes L.
, Shi, Huwenbo
, Khera, Amit V.
, Gazal, Steven
in
631/208/2489
/ 692/699
/ Accuracy
/ Agriculture
/ Animal Genetics and Genomics
/ Biobanks
/ Biomedical and Life Sciences
/ Biomedicine
/ Cancer Research
/ Estimates
/ Gene Function
/ Genome-Wide Association Study
/ Genomes
/ Human Genetics
/ Humans
/ Linkage Disequilibrium
/ Mapping
/ Methods
/ Multifactorial Inheritance - genetics
/ Polygenic inheritance
/ Polymorphism, Single Nucleotide - genetics
/ Populations
/ Risk
/ Risk Factors
/ Simulation
/ Training
2022
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Leveraging fine-mapping and multipopulation training data to improve cross-population polygenic risk scores
by
Kanai, Masahiro
, Peyrot, Wouter J.
, Weissbrod, Omer
, Martin, Alicia R.
, Okada, Yukinori
, Finucane, Hilary K.
, Price, Alkes L.
, Shi, Huwenbo
, Khera, Amit V.
, Gazal, Steven
in
631/208/2489
/ 692/699
/ Accuracy
/ Agriculture
/ Animal Genetics and Genomics
/ Biobanks
/ Biomedical and Life Sciences
/ Biomedicine
/ Cancer Research
/ Estimates
/ Gene Function
/ Genome-Wide Association Study
/ Genomes
/ Human Genetics
/ Humans
/ Linkage Disequilibrium
/ Mapping
/ Methods
/ Multifactorial Inheritance - genetics
/ Polygenic inheritance
/ Polymorphism, Single Nucleotide - genetics
/ Populations
/ Risk
/ Risk Factors
/ Simulation
/ Training
2022
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Leveraging fine-mapping and multipopulation training data to improve cross-population polygenic risk scores
by
Kanai, Masahiro
, Peyrot, Wouter J.
, Weissbrod, Omer
, Martin, Alicia R.
, Okada, Yukinori
, Finucane, Hilary K.
, Price, Alkes L.
, Shi, Huwenbo
, Khera, Amit V.
, Gazal, Steven
in
631/208/2489
/ 692/699
/ Accuracy
/ Agriculture
/ Animal Genetics and Genomics
/ Biobanks
/ Biomedical and Life Sciences
/ Biomedicine
/ Cancer Research
/ Estimates
/ Gene Function
/ Genome-Wide Association Study
/ Genomes
/ Human Genetics
/ Humans
/ Linkage Disequilibrium
/ Mapping
/ Methods
/ Multifactorial Inheritance - genetics
/ Polygenic inheritance
/ Polymorphism, Single Nucleotide - genetics
/ Populations
/ Risk
/ Risk Factors
/ Simulation
/ Training
2022
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Leveraging fine-mapping and multipopulation training data to improve cross-population polygenic risk scores
Journal Article
Leveraging fine-mapping and multipopulation training data to improve cross-population polygenic risk scores
2022
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Overview
Polygenic risk scores suffer reduced accuracy in non-European populations, exacerbating health disparities. We propose PolyPred, a method that improves cross-population polygenic risk scores by combining two predictors: a new predictor that leverages functionally informed fine-mapping to estimate causal effects (instead of tagging effects), addressing linkage disequilibrium differences, and BOLT-LMM, a published predictor. When a large training sample is available in the non-European target population, we propose PolyPred
+
, which further incorporates the non-European training data. We applied PolyPred to 49 diseases/traits in four UK Biobank populations using UK Biobank British training data, and observed relative improvements versus BOLT-LMM ranging from +7% in south Asians to +32% in Africans, consistent with simulations. We applied PolyPred
+
to 23 diseases/traits in UK Biobank east Asians using both UK Biobank British and Biobank Japan training data, and observed improvements of +24% versus BOLT-LMM and +12% versus PolyPred. Summary statistics-based analogs of PolyPred and PolyPred
+
attained similar improvements.
PolyPred and PolyPred
+
methods that leverage fine-mapping and non-European training data significantly improve cross-population polygenic prediction accuracy when applied to diseases and complex traits in UK Biobank populations.
Publisher
Nature Publishing Group US,Nature Publishing Group
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