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Sun, B.B.* ; Chiou, J.* ; Traylor, M.* ; Benner, C.* ; Hsu, Y.H.* ; Richardson, T.G.* ; Surendran, P.* ; Mahajan, A.* ; Robins, C.* ; Vasquez-Grinnell, S.G.* ; Hou, L.* ; Kvikstad, E.M.* ; Burren, O.S.* ; Davitte, J.* ; Ferber, K.L.* ; Gillies, C.E.* ; Hedman, A.K.* ; Hu, S.* ; Lin, T.* ; Mikkilineni, R.* ; Pendergrass, R.K.* ; Pickering, C.* ; Prins, B.* ; Baird, D.* ; Chen, C.Y.* ; Ward, L.D.* ; Deaton, A.M.* ; Welsh, S.* ; Willis, C.M.* ; Lehner, N. ; Arnold, M. ; Wörheide, M. ; Suhre, K.* ; Kastenmüller, G. ; Sethi, A.* ; Cule, M.* ; Raj, A.* ; Kang, H.M.* ; Burkitt-Gray, L.* ; Melamud, E.* ; Black, M.H.* ; Fauman, E.B.* ; Howson, J.M.M.* ; McCarthy, M.I.* ; Nioi, P.* ; Petrovski, S.* ; Scott, R.A.* ; Smith, E.N.* ; Szalma, S.* ; Waterworth, D.M.* ; Mitnaul, L.J.* ; Szustakowski, J.D.* ; Gibson, B.W.* ; Miller, M.R.* ; Whelan, C.D.*

Plasma proteomic associations with genetics and health in the UK Biobank.

Nature 622, 329-338 (2023)
Publ. Version/Full Text DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
The Pharma Proteomics Project is a precompetitive biopharmaceutical consortium characterizing the plasma proteomic profiles of 54,219 UK Biobank participants. Here we provide a detailed summary of this initiative, including technical and biological validations, insights into proteomic disease signatures, and prediction modelling for various demographic and health indicators. We present comprehensive protein quantitative trait locus (pQTL) mapping of 2,923 proteins that identifies 14,287 primary genetic associations, of which 81% are previously undescribed, alongside ancestry-specific pQTL mapping in non-European individuals. The study provides an updated characterization of the genetic architecture of the plasma proteome, contextualized with projected pQTL discovery rates as sample sizes and proteomic assay coverages increase over time. We offer extensive insights into trans pQTLs across multiple biological domains, highlight genetic influences on ligand–receptor interactions and pathway perturbations across a diverse collection of cytokines and complement networks, and illustrate long-range epistatic effects of ABO blood group and FUT2 secretor status on proteins with gastrointestinal tissue-enriched expression. We demonstrate the utility of these data for drug discovery by extending the genetic proxied effects of protein targets, such as PCSK9, on additional endpoints, and disentangle specific genes and proteins perturbed at loci associated with COVID-19 susceptibility. This public–private partnership provides the scientific community with an open-access proteomics resource of considerable breadth and depth to help to elucidate the biological mechanisms underlying proteo-genomic discoveries and accelerate the development of biomarkers, predictive models and therapeutics1.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Abo Blood-group; Deficiency; Proteins; Cohort; Risk
Language english
Publication Year 2023
HGF-reported in Year 2023
ISSN (print) / ISBN 0028-0836
e-ISSN 1476-4687
Journal Nature
Quellenangaben Volume: 622, Issue: 7982, Pages: 329-338 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed
Institute(s) Institute of Computational Biology (ICB)
POF-Topic(s) 30205 - Bioengineering and Digital Health
Research field(s) Enabling and Novel Technologies
PSP Element(s) G-503891-001
Grants leading internal activities at Olink
Janssen Pharmaceutical Companies of Johnson Johnson
Genentech
DOI 10.1038/s41586-023-06592-6
WOS ID 001085093000002
Scopus ID 85173243348
PubMed ID 37794186
Erfassungsdatum 2023-10-18
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