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Large-scale plasma proteomics comparisons through genetics and disease associations

Author

Listed:
  • Grimur Hjorleifsson Eldjarn

    (deCODE Genetics/Amgen)

  • Egil Ferkingstad

    (deCODE Genetics/Amgen)

  • Sigrun H. Lund

    (deCODE Genetics/Amgen
    University of Iceland)

  • Hannes Helgason

    (deCODE Genetics/Amgen
    University of Iceland)

  • Olafur Th. Magnusson

    (deCODE Genetics/Amgen)

  • Kristbjorg Gunnarsdottir

    (deCODE Genetics/Amgen)

  • Thorunn A. Olafsdottir

    (deCODE Genetics/Amgen)

  • Bjarni V. Halldorsson

    (deCODE Genetics/Amgen
    Reykjavik University)

  • Pall I. Olason

    (deCODE Genetics/Amgen)

  • Florian Zink

    (deCODE Genetics/Amgen)

  • Sigurjon A. Gudjonsson

    (deCODE Genetics/Amgen)

  • Gardar Sveinbjornsson

    (deCODE Genetics/Amgen)

  • Magnus I. Magnusson

    (deCODE Genetics/Amgen)

  • Agnar Helgason

    (deCODE Genetics/Amgen
    University of Iceland)

  • Asmundur Oddsson

    (deCODE Genetics/Amgen)

  • Gisli H. Halldorsson

    (deCODE Genetics/Amgen)

  • Magnus K. Magnusson

    (deCODE Genetics/Amgen
    University of Iceland)

  • Saedis Saevarsdottir

    (deCODE Genetics/Amgen
    University of Iceland)

  • Thjodbjorg Eiriksdottir

    (deCODE Genetics/Amgen)

  • Gisli Masson

    (deCODE Genetics/Amgen)

  • Hreinn Stefansson

    (deCODE Genetics/Amgen)

  • Ingileif Jonsdottir

    (deCODE Genetics/Amgen
    University of Iceland)

  • Hilma Holm

    (deCODE Genetics/Amgen)

  • Thorunn Rafnar

    (deCODE Genetics/Amgen)

  • Pall Melsted

    (deCODE Genetics/Amgen
    University of Iceland)

  • Jona Saemundsdottir

    (deCODE Genetics/Amgen)

  • Gudmundur L. Norddahl

    (deCODE Genetics/Amgen)

  • Gudmar Thorleifsson

    (deCODE Genetics/Amgen)

  • Magnus O. Ulfarsson

    (deCODE Genetics/Amgen
    University of Iceland)

  • Daniel F. Gudbjartsson

    (deCODE Genetics/Amgen
    University of Iceland)

  • Unnur Thorsteinsdottir

    (deCODE Genetics/Amgen
    University of Iceland)

  • Patrick Sulem

    (deCODE Genetics/Amgen)

  • Kari Stefansson

    (deCODE Genetics/Amgen
    University of Iceland)

Abstract

High-throughput proteomics platforms measuring thousands of proteins in plasma combined with genomic and phenotypic information have the power to bridge the gap between the genome and diseases. Here we performed association studies of Olink Explore 3072 data generated by the UK Biobank Pharma Proteomics Project1 on plasma samples from more than 50,000 UK Biobank participants with phenotypic and genotypic data, stratifying on British or Irish, African and South Asian ancestries. We compared the results with those of a SomaScan v4 study on plasma from 36,000 Icelandic people2, for 1,514 of whom Olink data were also available. We found modest correlation between the two platforms. Although cis protein quantitative trait loci were detected for a similar absolute number of assays on the two platforms (2,101 on Olink versus 2,120 on SomaScan), the proportion of assays with such supporting evidence for assay performance was higher on the Olink platform (72% versus 43%). A considerable number of proteins had genomic associations that differed between the platforms. We provide examples where differences between platforms may influence conclusions drawn from the integration of protein levels with the study of diseases. We demonstrate how leveraging the diverse ancestries of participants in the UK Biobank helps to detect novel associations and refine genomic location. Our results show the value of the information provided by the two most commonly used high-throughput proteomics platforms and demonstrate the differences between them that at times provides useful complementarity.

Suggested Citation

  • Grimur Hjorleifsson Eldjarn & Egil Ferkingstad & Sigrun H. Lund & Hannes Helgason & Olafur Th. Magnusson & Kristbjorg Gunnarsdottir & Thorunn A. Olafsdottir & Bjarni V. Halldorsson & Pall I. Olason & , 2023. "Large-scale plasma proteomics comparisons through genetics and disease associations," Nature, Nature, vol. 622(7982), pages 348-358, October.
  • Handle: RePEc:nat:nature:v:622:y:2023:i:7982:d:10.1038_s41586-023-06563-x
    DOI: 10.1038/s41586-023-06563-x
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    Cited by:

    1. Chirag Krishna & Joshua Chiou & Saori Sakaue & Joyce B. Kang & Stephen M. Christensen & Isac Lee & Melis Atalar Aksit & Hye In Kim & David Schack & Soumya Raychaudhuri & Daniel Ziemek & Xinli Hu, 2024. "The influence of HLA genetic variation on plasma protein expression," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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