Large-scale plasma proteomics comparisons through genetics and disease associations.
Autor: | Eldjarn GH; deCODE Genetics/Amgen, Reykjavik, Iceland., Ferkingstad E; deCODE Genetics/Amgen, Reykjavik, Iceland., Lund SH; deCODE Genetics/Amgen, Reykjavik, Iceland.; School of Engineering and Natural Sciences, University of Iceland, Reykjavik, Iceland., Helgason H; deCODE Genetics/Amgen, Reykjavik, Iceland.; School of Engineering and Natural Sciences, University of Iceland, Reykjavik, Iceland., Magnusson OT; deCODE Genetics/Amgen, Reykjavik, Iceland., Gunnarsdottir K; deCODE Genetics/Amgen, Reykjavik, Iceland., Olafsdottir TA; deCODE Genetics/Amgen, Reykjavik, Iceland., Halldorsson BV; deCODE Genetics/Amgen, Reykjavik, Iceland.; School of Technology, Reykjavik University, Reykjavik, Iceland., Olason PI; deCODE Genetics/Amgen, Reykjavik, Iceland., Zink F; deCODE Genetics/Amgen, Reykjavik, Iceland., Gudjonsson SA; deCODE Genetics/Amgen, Reykjavik, Iceland., Sveinbjornsson G; deCODE Genetics/Amgen, Reykjavik, Iceland., Magnusson MI; deCODE Genetics/Amgen, Reykjavik, Iceland., Helgason A; deCODE Genetics/Amgen, Reykjavik, Iceland.; Department of Anthropology, University of Iceland, Reykjavik, Iceland., Oddsson A; deCODE Genetics/Amgen, Reykjavik, Iceland., Halldorsson GH; deCODE Genetics/Amgen, Reykjavik, Iceland., Magnusson MK; deCODE Genetics/Amgen, Reykjavik, Iceland.; Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland., Saevarsdottir S; deCODE Genetics/Amgen, Reykjavik, Iceland.; Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland., Eiriksdottir T; deCODE Genetics/Amgen, Reykjavik, Iceland., Masson G; deCODE Genetics/Amgen, Reykjavik, Iceland., Stefansson H; deCODE Genetics/Amgen, Reykjavik, Iceland., Jonsdottir I; deCODE Genetics/Amgen, Reykjavik, Iceland.; Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland., Holm H; deCODE Genetics/Amgen, Reykjavik, Iceland., Rafnar T; deCODE Genetics/Amgen, Reykjavik, Iceland., Melsted P; deCODE Genetics/Amgen, Reykjavik, Iceland.; School of Engineering and Natural Sciences, University of Iceland, Reykjavik, Iceland., Saemundsdottir J; deCODE Genetics/Amgen, Reykjavik, Iceland., Norddahl GL; deCODE Genetics/Amgen, Reykjavik, Iceland., Thorleifsson G; deCODE Genetics/Amgen, Reykjavik, Iceland., Ulfarsson MO; deCODE Genetics/Amgen, Reykjavik, Iceland.; Faculty of Electrical and Computer Engineering, University of Iceland, Reykjavik, Iceland., Gudbjartsson DF; deCODE Genetics/Amgen, Reykjavik, Iceland.; School of Engineering and Natural Sciences, University of Iceland, Reykjavik, Iceland., Thorsteinsdottir U; deCODE Genetics/Amgen, Reykjavik, Iceland.; Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland., Sulem P; deCODE Genetics/Amgen, Reykjavik, Iceland. patrick.sulem@decode.is., Stefansson K; deCODE Genetics/Amgen, Reykjavik, Iceland. kstefans@decode.is.; Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland. kstefans@decode.is. |
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Jazyk: | angličtina |
Zdroj: | Nature [Nature] 2023 Oct; Vol. 622 (7982), pp. 348-358. Date of Electronic Publication: 2023 Oct 04. |
DOI: | 10.1038/s41586-023-06563-x |
Abstrakt: | 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 Project 1 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 people 2 , 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. (© 2023. The Author(s).) |
Databáze: | MEDLINE |
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