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Genetic architecture of host proteins involved in SARS-CoV-2 infection

Author

Listed:
  • Maik Pietzner

    (MRC Epidemiology Unit, University of Cambridge)

  • Eleanor Wheeler

    (MRC Epidemiology Unit, University of Cambridge)

  • Julia Carrasco-Zanini

    (MRC Epidemiology Unit, University of Cambridge)

  • Johannes Raffler

    (Institute of Computational Biology, Helmholtz Zentrum München – German Research Center for Environmental Health)

  • Nicola D. Kerrison

    (MRC Epidemiology Unit, University of Cambridge)

  • Erin Oerton

    (MRC Epidemiology Unit, University of Cambridge)

  • Victoria P. W. Auyeung

    (MRC Epidemiology Unit, University of Cambridge)

  • Jian’an Luan

    (MRC Epidemiology Unit, University of Cambridge)

  • Chris Finan

    (University College London
    UCL BHF Research Accelerator centre)

  • Juan P. Casas

    (Brigham and Women’s Hospital, Harvard Medical School
    VA Boston Healthcare System)

  • Rachel Ostroff

    (SomaLogic, Inc.)

  • Steve A. Williams

    (SomaLogic, Inc.)

  • Gabi Kastenmüller

    (Institute of Computational Biology, Helmholtz Zentrum München – German Research Center for Environmental Health)

  • Markus Ralser

    (The Francis Crick Institute
    Charité University Medicine)

  • Eric R. Gamazon

    (MRC Epidemiology Unit, University of Cambridge
    Vanderbilt University Medical Center)

  • Nicholas J. Wareham

    (MRC Epidemiology Unit, University of Cambridge
    Wellcome Genome Campus and University of Cambridge)

  • Aroon D. Hingorani

    (University College London
    UCL BHF Research Accelerator centre
    University College London)

  • Claudia Langenberg

    (MRC Epidemiology Unit, University of Cambridge
    The Francis Crick Institute
    Wellcome Genome Campus and University of Cambridge
    Charité University Medicine)

Abstract

Understanding the genetic architecture of host proteins interacting with SARS-CoV-2 or mediating the maladaptive host response to COVID-19 can help to identify new or repurpose existing drugs targeting those proteins. We present a genetic discovery study of 179 such host proteins among 10,708 individuals using an aptamer-based technique. We identify 220 host DNA sequence variants acting in cis (MAF 0.01-49.9%) and explaining 0.3-70.9% of the variance of 97 of these proteins, including 45 with no previously known protein quantitative trait loci (pQTL) and 38 encoding current drug targets. Systematic characterization of pQTLs across the phenome identified protein-drug-disease links and evidence that putative viral interaction partners such as MARK3 affect immune response. Our results accelerate the evaluation and prioritization of new drug development programmes and repurposing of trials to prevent, treat or reduce adverse outcomes. Rapid sharing and detailed interrogation of results is facilitated through an interactive webserver ( https://omicscience.org/apps/covidpgwas/ ).

Suggested Citation

  • Maik Pietzner & Eleanor Wheeler & Julia Carrasco-Zanini & Johannes Raffler & Nicola D. Kerrison & Erin Oerton & Victoria P. W. Auyeung & Jian’an Luan & Chris Finan & Juan P. Casas & Rachel Ostroff & S, 2020. "Genetic architecture of host proteins involved in SARS-CoV-2 infection," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19996-z
    DOI: 10.1038/s41467-020-19996-z
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    Citations

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    Cited by:

    1. Grace Png & Andrei Barysenka & Linda Repetto & Pau Navarro & Xia Shen & Maik Pietzner & Eleanor Wheeler & Nicholas J. Wareham & Claudia Langenberg & Emmanouil Tsafantakis & Maria Karaleftheri & George, 2021. "Mapping the serum proteome to neurological diseases using whole genome sequencing," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    2. Lina Cai & Tomas Gonzales & Eleanor Wheeler & Nicola D. Kerrison & Felix R. Day & Claudia Langenberg & John R. B. Perry & Soren Brage & Nicholas J. Wareham, 2023. "Causal associations between cardiorespiratory fitness and type 2 diabetes," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    3. Maik Pietzner & Eleanor Wheeler & Julia Carrasco-Zanini & Nicola D. Kerrison & Erin Oerton & Mine Koprulu & Jian’an Luan & Aroon D. Hingorani & Steve A. Williams & Nicholas J. Wareham & Claudia Langen, 2021. "Synergistic insights into human health from aptamer- and antibody-based proteomic profiling," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    4. Danni A. Gadd & Robert F. Hillary & Daniel L. McCartney & Liu Shi & Aleks Stolicyn & Neil A. Robertson & Rosie M. Walker & Robert I. McGeachan & Archie Campbell & Shen Xueyi & Miruna C. Barbu & Claire, 2022. "Integrated methylome and phenome study of the circulating proteome reveals markers pertinent to brain health," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    5. Fengzhe Xu & Evan Yi-Wen Yu & Xue Cai & Liang Yue & Li-peng Jing & Xinxiu Liang & Yuanqing Fu & Zelei Miao & Min Yang & Menglei Shuai & Wanglong Gou & Congmei Xiao & Zhangzhi Xue & Yuting Xie & Sainan, 2023. "Genome-wide genotype-serum proteome mapping provides insights into the cross-ancestry differences in cardiometabolic disease susceptibility," Nature Communications, Nature, vol. 14(1), pages 1-12, December.

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