Ancestry deconvolution and partial polygenic score can improve susceptibility predictions in recently admixed individuals

Polygenic Scores (PSs) describe the genetic component of an individual’s quantitative phenotype or their susceptibility to diseases with a genetic basis. Currently, PSs rely on population-dependent contributions of many associated alleles, with limited applicability to understudied populations and r...

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Vydáno v:Nature communications Ročník 11; číslo 1; s. 1628 - 9
Hlavní autoři: Marnetto, Davide, Pärna, Katri, Läll, Kristi, Molinaro, Ludovica, Montinaro, Francesco, Haller, Toomas, Metspalu, Mait, Mägi, Reedik, Fischer, Krista, Pagani, Luca
Médium: Journal Article
Jazyk:angličtina
Vydáno: London Nature Publishing Group UK 02.04.2020
Nature Publishing Group
Nature Portfolio
Témata:
631/114/2413
631/208/205
631/208/457/649
Bias
Deconvolution
Genealogy
Genetic Predisposition to Disease
Genetics, Population
Genomes
Genotype
Humanities and Social Sciences
Humans
Models, Genetic
multidisciplinary
Multifactorial Inheritance
Phenotype
Phenotypes
Polygenic inheritance
Population
Population genetics
Populations
Precision medicine
Predictions
Science
Science (multidisciplinary)
ISSN:2041-1723, 2041-1723
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Popis
Shrnutí:Polygenic Scores (PSs) describe the genetic component of an individual’s quantitative phenotype or their susceptibility to diseases with a genetic basis. Currently, PSs rely on population-dependent contributions of many associated alleles, with limited applicability to understudied populations and recently admixed individuals. Here we introduce a combination of local ancestry deconvolution and partial PS computation to account for the population-specific nature of the association signals in individuals with admixed ancestry. We demonstrate partial PS to be a proxy for the total PS and that a portion of the genome is enough to improve susceptibility predictions for the traits we test. By combining partial PSs from different populations, we are able to improve trait predictability in admixed individuals with some European ancestry. These results may extend the applicability of PSs to subjects with a complex history of admixture, where current methods cannot be applied. Polygenic scores are believed to hold future promise for trait prediction and personalized medicine, but are sensitive to demographic history. Here, Marnetto et al . develop partial polygenic scores supplemented with local ancestry deconvolution which improves prediction accuracy into recently admixed European populations.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-020-15464-w