Large-scale plasma proteomics comparisons through genetics and disease associations
Grimur Hjorleifsson Eldjarn,
Egil Ferkingstad,
Sigrun H. Lund,
Hannes Helgason,
Olafur Th. Magnusson,
Kristbjorg Gunnarsdottir,
Thorunn A. Olafsdottir,
Bjarni V. Halldorsson,
Pall I. Olason,
Florian Zink,
Sigurjon A. Gudjonsson,
Gardar Sveinbjornsson,
Magnus I. Magnusson,
Agnar Helgason,
Asmundur Oddsson,
Gisli H. Halldorsson,
Magnus K. Magnusson,
Saedis Saevarsdottir,
Thjodbjorg Eiriksdottir,
Gisli Masson,
Hreinn Stefansson,
Ingileif Jonsdottir,
Hilma Holm,
Thorunn Rafnar,
Pall Melsted,
Jona Saemundsdottir,
Gudmundur L. Norddahl,
Gudmar Thorleifsson,
Magnus O. Ulfarsson,
Daniel F. Gudbjartsson,
Unnur Thorsteinsdottir,
Patrick Sulem () and
Kari Stefansson ()
Additional contact information
Grimur Hjorleifsson Eldjarn: deCODE Genetics/Amgen
Egil Ferkingstad: deCODE Genetics/Amgen
Sigrun H. Lund: deCODE Genetics/Amgen
Hannes Helgason: deCODE Genetics/Amgen
Olafur Th. Magnusson: deCODE Genetics/Amgen
Kristbjorg Gunnarsdottir: deCODE Genetics/Amgen
Thorunn A. Olafsdottir: deCODE Genetics/Amgen
Bjarni V. Halldorsson: deCODE Genetics/Amgen
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
Asmundur Oddsson: deCODE Genetics/Amgen
Gisli H. Halldorsson: deCODE Genetics/Amgen
Magnus K. Magnusson: deCODE Genetics/Amgen
Saedis Saevarsdottir: deCODE Genetics/Amgen
Thjodbjorg Eiriksdottir: deCODE Genetics/Amgen
Gisli Masson: deCODE Genetics/Amgen
Hreinn Stefansson: deCODE Genetics/Amgen
Ingileif Jonsdottir: deCODE Genetics/Amgen
Hilma Holm: deCODE Genetics/Amgen
Thorunn Rafnar: deCODE Genetics/Amgen
Pall Melsted: deCODE Genetics/Amgen
Jona Saemundsdottir: deCODE Genetics/Amgen
Gudmundur L. Norddahl: deCODE Genetics/Amgen
Gudmar Thorleifsson: deCODE Genetics/Amgen
Magnus O. Ulfarsson: deCODE Genetics/Amgen
Daniel F. Gudbjartsson: deCODE Genetics/Amgen
Unnur Thorsteinsdottir: deCODE Genetics/Amgen
Patrick Sulem: deCODE Genetics/Amgen
Kari Stefansson: deCODE Genetics/Amgen
Nature, 2023, vol. 622, issue 7982, 348-358
Abstract:
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.
Date: 2023
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DOI: 10.1038/s41586-023-06563-x
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