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Benjamin B. Sun, Joshua Chiou, Matthew Traylor, Christian Benner, Yi‐Hsiang Hsu, Tom G. Richardson, Praveen Surendran, Anubha Mahajan, Chloe Robins, Steven G. Grinnell and 54 more
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 therapeutics 1 .
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Sun, B. B., Chiou, J., Traylor, M., Benner, C., Hsu, Y., Richardson, T. G., Surendran, P., Mahajan, A., Robins, C., Grinnell, S. G., Hou, L., Kvikstad, E. M., Burren, O. S., Davitte, J., Ferber, K. L., Gillies, C. E., Hedman, Å. K., Hu, S., Lin, T.-C., … Whelan, C. D. (2023). Plasma proteomic associations with genetics and health in the UK Biobank. Nature, 622(7982), 329–338. https://doi.org/10.1038/s41586-023-06592-6
Sun, Benjamin B., et al. "Plasma proteomic associations with genetics and health in the UK Biobank." Nature, vol. 622, no. 7982, 2023, pp. 329–338, https://doi.org/10.1038/s41586-023-06592-6.
Sun, Benjamin B., Joshua Chiou, Matthew Traylor, Christian Benner, Yi‐Hsiang Hsu, Tom G. Richardson, Praveen Surendran, et al. "Plasma proteomic associations with genetics and health in the UK Biobank." Nature 622, no. 7982 (2023): 329–338. https://doi.org/10.1038/s41586-023-06592-6.
Sun B. B., Chiou J., Traylor M. [и др.] Plasma proteomic associations with genetics and health in the UK Biobank // Nature. — 2023. — Vol. 622, № 7982. — P. 329–338. — URL: https://doi.org/10.1038/s41586-023-06592-6
@article{sun2023plasma,
title = {{Plasma proteomic associations with genetics and health in the UK Biobank}},
author = {Benjamin B. Sun and Joshua Chiou and Matthew Traylor and Christian Benner and Yi‐Hsiang Hsu and Tom G. Richardson and Praveen Surendran and Anubha Mahajan and Chloe Robins and Steven G. Grinnell and Liping Hou and Erika M. Kvikstad and Oliver S. Burren and Jonathan Davitte and Kyle L. Ferber and Christopher E. Gillies and Åsa K. Hedman and Sile Hu and Tin-Chi Lin and Rajesh Mikkilineni and Rion K. Pendergrass and Corran Pickering and Bram Peter Prins and Denis A. Baird and Chia‐Yen Chen and Lucas D. Ward and Aimée M. Deaton and Samantha Welsh and Carissa M. Willis and Nick Lehner and Matthias Arnold and Maria A. Wörheide and Karsten Suhre and Gabi Kastenmüller and Anurag Sethi and Madeleine Cule and Anil Raj and Alnylam Human Genetics and AstraZeneca Genomics Initiative and Biogen Biobank Team and Bristol Myers Squibb and Genentech Human Genetics and GlaxoSmithKline Genomic Sciences and Pfizer Integrative Biology and Population Analytics of Janssen Data Sciences and Hyun Ming Kang and Lucy Burkitt-Gray and Eugene Melamud and Mary Helen Black and Eric B. Fauman and Joanna M. M. Howson and Hyun Min Kang and Mark I. McCarthy and Paul Nioi and Slavé Petrovski and Robert A. Scott and Erin N. Smith and Sándor Szalma and Dawn M. Waterworth and Lyndon J. Mitnaul and Joseph D. Szustakowski and Bradford W. Gibson and Melissa R. Miller and Christopher D. Whelan},
journal = {Nature},
year = {2023},
volume = {622},
number = {7982},
pages = {329--338},
doi = {10.1038/s41586-023-06592-6},
url = {https://doi.org/10.1038/s41586-023-06592-6}
}TY - JOUR AU - Sun, Benjamin B. AU - Chiou, Joshua AU - Traylor, Matthew AU - Benner, Christian AU - Hsu, Yi‐Hsiang AU - Richardson, Tom G. AU - Surendran, Praveen AU - Mahajan, Anubha AU - Robins, Chloe AU - Grinnell, Steven G. AU - Hou, Liping AU - Kvikstad, Erika M. AU - Burren, Oliver S. AU - Davitte, Jonathan AU - Ferber, Kyle L. AU - Gillies, Christopher E. AU - Hedman, Åsa K. AU - Hu, Sile AU - Lin, Tin-Chi AU - Mikkilineni, Rajesh AU - Pendergrass, Rion K. AU - Pickering, Corran AU - Prins, Bram Peter AU - Baird, Denis A. AU - Chen, Chia‐Yen AU - Ward, Lucas D. AU - Deaton, Aimée M. AU - Welsh, Samantha AU - Willis, Carissa M. AU - Lehner, Nick AU - Arnold, Matthias AU - Wörheide, Maria A. AU - Suhre, Karsten AU - Kastenmüller, Gabi AU - Sethi, Anurag AU - Cule, Madeleine AU - Raj, Anil AU - Genetics, Alnylam Human AU - Initiative, AstraZeneca Genomics AU - Biogen Biobank Team AU - Squibb, Bristol Myers AU - Genetics, Genentech Human AU - Sciences, GlaxoSmithKline Genomic AU - Biology, Pfizer Integrative AU - Sciences, Population Analytics of Janssen Data AU - Kang, Hyun Ming AU - Burkitt-Gray, Lucy AU - Melamud, Eugene AU - Black, Mary Helen AU - Fauman, Eric B. AU - Howson, Joanna M. M. AU - Kang, Hyun Min AU - McCarthy, Mark I. AU - Nioi, Paul AU - Petrovski, Slavé AU - Scott, Robert A. AU - Smith, Erin N. AU - Szalma, Sándor AU - Waterworth, Dawn M. AU - Mitnaul, Lyndon J. AU - Szustakowski, Joseph D. AU - Gibson, Bradford W. AU - Miller, Melissa R. AU - Whelan, Christopher D. TI - Plasma proteomic associations with genetics and health in the UK Biobank JO - Nature VL - 622 IS - 7982 SP - 329 EP - 338 PY - 2023 DA - 2023/10/04 DO - 10.1038/s41586-023-06592-6 UR - https://doi.org/10.1038/s41586-023-06592-6 ER -
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