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Mapping the serum proteome to neurological diseases using whole genome sequencing

Author

Listed:
  • Grace Png

    (Helmholtz Zentrum München – German Research Center for Environmental Health
    Technical University of Munich and Klinikum Rechts der Isar)

  • Andrei Barysenka

    (Helmholtz Zentrum München – German Research Center for Environmental Health)

  • Linda Repetto

    (University of Edinburgh)

  • Pau Navarro

    (University of Edinburgh)

  • Xia Shen

    (University of Edinburgh
    Fudan University
    Karolinska Institute)

  • Maik Pietzner

    (University of Cambridge)

  • Eleanor Wheeler

    (University of Cambridge)

  • Nicholas J. Wareham

    (University of Cambridge)

  • Claudia Langenberg

    (University of Cambridge
    Computational Medicine, Berlin Institute of Health (BIH), Charité University Medicine)

  • Emmanouil Tsafantakis

    (Anogia Medical Centre)

  • Maria Karaleftheri

    (Echinos Medical Centre)

  • George Dedoussis

    (School of Health Science and Education, Harokopio University of Athens)

  • Anders Mälarstig

    (Karolinska Institute
    Emerging Science & Innovation, Pfizer Worldwide Research, Development and Medical)

  • James F. Wilson

    (University of Edinburgh
    University of Edinburgh)

  • Arthur Gilly

    (Helmholtz Zentrum München – German Research Center for Environmental Health)

  • Eleftheria Zeggini

    (Helmholtz Zentrum München – German Research Center for Environmental Health
    Technical University of Munich and Klinikum Rechts der Isar)

Abstract

Despite the increasing global burden of neurological disorders, there is a lack of effective diagnostic and therapeutic biomarkers. Proteins are often dysregulated in disease and have a strong genetic component. Here, we carry out a protein quantitative trait locus analysis of 184 neurologically-relevant proteins, using whole genome sequencing data from two isolated population-based cohorts (N = 2893). In doing so, we elucidate the genetic landscape of the circulating proteome and its connection to neurological disorders. We detect 214 independently-associated variants for 107 proteins, the majority of which (76%) are cis-acting, including 114 variants that have not been previously identified. Using two-sample Mendelian randomisation, we identify causal associations between serum CD33 and Alzheimer’s disease, GPNMB and Parkinson’s disease, and MSR1 and schizophrenia, describing their clinical potential and highlighting drug repurposing opportunities.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27387-1
    DOI: 10.1038/s41467-021-27387-1
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    References listed on IDEAS

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