Polygenic scoring accuracy varies across the genetic ancestry continuum in all human populations Article Swipe
Yi Ding
,
Kangcheng Hou
,
Ziqi Xu
,
Aditya Pimplaskar
,
Ella Petter
,
Kristin Boulier
,
Florian Privé
,
Bjarni J. Vilhjálmsson
,
Loes M. Olde Loohuis
,
Bogdan Paşaniuc
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1101/2022.09.28.509988
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1101/2022.09.28.509988
Polygenic scores (PGS) have limited portability across different groupings of individuals (e.g., by genetic ancestries and/or social determinants of health), preventing their equitable use. PGS portability has typically been assessed using a single aggregate population-level statistic (e.g., R 2 ), ignoring inter-individual variation within the population. Here we evaluate PGS accuracy at individual-level resolution, independent of its annotated genetic ancestries. We show that PGS accuracy varies between individuals across the genetic ancestry continuum in all ancestries, even within traditionally “homogeneous” genetic ancestry clusters. Using a large and diverse Los Angeles biobank (ATLAS, N= 36,778) along with the UK Biobank (UKBB, N= 487,409), we show that PGS accuracy decreases along a continuum of genetic ancestries in all considered populations and the trend is well-captured by a continuous measure of genetic distance (GD) from the PGS training data; Pearson correlation of −0.95 between GD and PGS accuracy averaged across 84 traits. When applying PGS models trained in UKBB “white British” individuals to European-ancestry individuals of ATLAS, individuals in the highest GD decile have 14% lower accuracy relative to the lowest decile; notably the lowest GD decile of Hispanic/Latino American ancestry individuals showed similar PGS performance as the highest GD decile of European ancestry ATLAS individuals. GD is significantly correlated with PGS estimates themselves for 82 out of 84 traits, further emphasizing the importance of incorporating the continuum of genetic ancestry in PGS interpretation. Our results highlight the need for moving away from discrete genetic ancestry clusters towards the continuum of genetic ancestries when considering PGS and their applications.
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- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2022.09.28.509988
- https://www.biorxiv.org/content/biorxiv/early/2022/09/29/2022.09.28.509988.full.pdf
- OA Status
- green
- Cited By
- 17
- References
- 45
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4298144476
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Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4298144476Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1101/2022.09.28.509988Digital Object Identifier
- Title
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Polygenic scoring accuracy varies across the genetic ancestry continuum in all human populationsWork title
- Type
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preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
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2022Year of publication
- Publication date
-
2022-09-29Full publication date if available
- Authors
-
Yi Ding, Kangcheng Hou, Ziqi Xu, Aditya Pimplaskar, Ella Petter, Kristin Boulier, Florian Privé, Bjarni J. Vilhjálmsson, Loes M. Olde Loohuis, Bogdan PaşaniucList of authors in order
- Landing page
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https://doi.org/10.1101/2022.09.28.509988Publisher landing page
- PDF URL
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https://www.biorxiv.org/content/biorxiv/early/2022/09/29/2022.09.28.509988.full.pdfDirect link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
-
https://www.biorxiv.org/content/biorxiv/early/2022/09/29/2022.09.28.509988.full.pdfDirect OA link when available
- Concepts
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Genetic genealogy, Decile, Biobank, Population, Genetic variation, Evolutionary biology, Demography, Genetic admixture, Biology, Genetics, Geography, Statistics, Mathematics, SociologyTop concepts (fields/topics) attached by OpenAlex
- Cited by
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17Total citation count in OpenAlex
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2025: 2, 2024: 5, 2023: 8, 2022: 2Per-year citation counts (last 5 years)
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45Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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