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PreprintCited by 16Genetic Associations and EpidemiologyGenetic Mapping and Diversity in Plants and AnimalsGenetic and phenotypic traits in livestock

Ancestry diversity in the genetic determinants of the human plasma proteome enhances identification of potential drug targets

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Pozarickij, Alfred, Said, Saredo, Lin, Kuang, Morris, Sam, Edris, Ahmed, Iona, Andri, Kartsonaki, Christiana, Wright, Neil +21 more·2023·medRxiv
DOI 10.1101/2023.11.13.23298365
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Abstract

The proteome is fundamental to human biology and health but little is known about ancestral diversity of its genetic determinants. In GWAS of plasma levels of 2,923 proteins in 3,974 Chinese adults, we identified pQTLs for 1,784 proteins, including 1,312 cis -pQTLs for 1,264 proteins. Fine-mapping identified 3,475 credible sets for independent pQTLs, 36% of which were distinct from those identified in European adults as assessed by three different methods. In phenome-wide MR analyses, 59 disease associations were in strong LD (r 2 >0.95) with a cis -pQTL sentinel variant, including 26 with strong evidence of colocalisation (PP.H4>0.9) and 34 not identified in previous similar European studies. Evaluation of current drug development identified 8 confirmed therapeutic targets, 8 potential repurposing targets, and 19 potential novel targets (13 not previously reported in Europeans). The findings demonstrate the importance of extending proteogenomic studies to non-European ancestry populations to identify potential novel drug targets for major diseases.

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Crossref · 10.1101/2023.11.13.23298365

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  • Protein quantitative trait loci (pQTL) are commonly detected in large-scale studies.

    “Protein quantitative trait loci (pQTL), or associations between circulating protein abundances and genetic variants either within or nearby (cis-) to the protein-encoding gene or elsewhere in the genome (trans-), are commonly detected in large-scale studies1–6.”

    From Cross-ancestry comparison of aptamer and antibody protein measures (2026) · cites this paper as [3]

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Research works printed but not linked: 18

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Authors
Pozarickij, A., Said, S., Lin, K., Morris, S., Edris, A., Iona, A., Kartsonaki, C., Wright, N., Yao, P., Fry, H., Chen, Y., Yang, L., Du, H., Bennett, D., Avery, D., Schmidt, D. V., Lv, J., Yu, C., Sun, D., Pei, P., Chen, J., Hill, M., Peto, R., Collins, R., Clarke, R., Li, L., Millwood, I. Y., Chen, Z., & Walters, R. G.
Affiliations
  • University of Oxford (GB)
  • Peking University (CN)
  • China National Center for Food Safety Risk Assessment (CN)
Corresponding author
  • Chen, Zhengming
  • Walters, Robin G
ORCID
Venue
medRxiv
Publisher
openRxiv
Published
2023-11-13
DOI
10.1101/2023.11.13.23298365
OpenAlex
W4388627051
Cited by
16
References
6
Citations by year
2026: 7 · 2025: 6 · 2024: 3
Type
posted content
Language
en
Open access
Licence
Locations
medRxiv (acceptedVersion, cc-by)
Funders
  • GlaxoSmithKline
  • Wellcome Trust (212946/Z/18/Z, 202922/Z/16/Z, 088158/Z/09/Z, 104085/Z/14/Z)
  • Cancer Research UK (A29186, 088158/Z/09/Z, MC_UU_00017/1, 2016YFC0900500, CH/1996001/9454, C500/A16896, 212946/Z/18/Z, C16077 /A29186, 104085/Z/14/Z, 202922/Z/16/Z)
  • National Institute for Health and Care Research
  • British Heart Foundation (104085/Z/14/Z, CH/1996001/9454, 18/23/33512, 088158/Z/09/Z, C16077/A29186, 2016YFC0900500, C500/A16896, MC_UU_00017/1, 212946/Z/18/Z, 202922/Z/16/Z)
  • University of Oxford (104085/Z/14/Z, 202922/Z/16/Z, 212946/Z/18/Z, 088158/Z/09/Z)
  • National Natural Science Foundation of China (2016YFC0900500, 104085/Z/14/Z, 212946/Z/18/Z, 202922/Z/16/Z, 088158/Z/09/Z, 82192904, C500/A16896, 82192901, C16077/A29186, MC_UU_00017/1, CH/1996001/9454, 82192900)
  • Novo Nordisk
  • Chinese Center for Disease Control and Prevention
  • Centers for Disease Control and Prevention
  • Medical Research Council (MC_UU_00017/1, MC_PC_13049, C500/A16896, 2016YFC0900500, MC_PC_14135, 104085/Z/14/Z, CH/1996001/9454, 088158/Z/09/Z, 212946/Z/18/Z, 202922/Z/16/Z, MC_U137686851, MC_UU_12026/2, C16077/A29186)
  • National Key Research and Development Program of China (MC_UU_00017/1, 088158/Z/09/Z, 2016YFC0900500, 202922/Z/16/Z, 104085/Z/14/Z, CH/1996001/9454, C16077/A29186, 212946/Z/18/Z, C500/A16896)
  • Biomedical Research Council
  • Health Data Research UK
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and phenotypic traits in livestock
Keywords
plasma proteome, protein quantitative trait loci, cis-pQTL, ancestry diversity, Chinese population, non-European ancestry, fine mapping, phenome-wide Mendelian randomization, drug target identification, drug repurposing, colocalization, proteogenomics

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