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The genetic landscape of neuro-related proteins in human plasma

Author

Listed:
  • Linda Repetto

    (Sun Yat-sen University
    Fudan University
    University of Edinburgh
    Fondazione Human Technopole)

  • Jiantao Chen

    (Sun Yat-sen University
    Fudan University
    Fudan University)

  • Zhijian Yang

    (Sun Yat-sen University
    Fudan University
    Fudan University
    Karolinska Institutet)

  • Ranran Zhai

    (Sun Yat-sen University
    Fudan University
    Fudan University
    Karolinska Institutet)

  • Paul R. H. J. Timmers

    (University of Edinburgh
    University of Edinburgh)

  • Xiao Feng

    (Fudan University
    Fudan University)

  • Ting Li

    (Sun Yat-sen University
    Fudan University
    Fudan University)

  • Yue Yao

    (Fudan University
    Fudan University)

  • Denis Maslov

    (Lomonosov Moscow State University)

  • Anna Timoshchuk

    (Lomonosov Moscow State University)

  • Fengyu Tu

    (Sun Yat-sen University)

  • Emma L. Twait

    (University Medical Center Utrecht and Utrecht University)

  • Sebastian May-Wilson

    (University of Edinburgh)

  • Marisa D. Muckian

    (University of Edinburgh)

  • Bram P. Prins

    (University of Cambridge)

  • Grace Png

    (Helmholtz Zentrum München—German Research Center for Environmental Health
    TUM School of Medicine and Health)

  • Charles Kooperberg

    (Fred Hutchinson Cancer Center)

  • Åsa Johansson

    (Uppsala University)

  • Robert F. Hillary

    (The University of Edinburgh)

  • Eleanor Wheeler

    (University of Cambridge School of Clinical Medicine)

  • Lu Pan

    (Karolinska Institutet)

  • Yazhou He

    (Sichuan University)

  • Sofia Klasson

    (University of Gothenburg)

  • Shahzad Ahmad

    (Erasmus MC)

  • James E. Peters

    (Imperial College London)

  • Arthur Gilly

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

  • Maria Karaleftheri

    (Echinos Medical Centre)

  • Emmanouil Tsafantakis

    (Anogia Medical Centre)

  • Jeffrey Haessler

    (Fred Hutchinson Cancer Center)

  • Ulf Gyllensten

    (Uppsala University)

  • Sarah E. Harris

    (University of Edinburgh)

  • Nicholas J. Wareham

    (University of Cambridge School of Clinical Medicine)

  • Andreas Göteson

    (The Sahlgrenska Academy at the University of Gothenburg)

  • Cecilia Lagging

    (University of Gothenburg
    Sahlgrenska University Hospital)

  • Mohammad Arfan Ikram

    (Erasmus MC)

  • Cornelia M. Duijn

    (Erasmus MC)

  • Christina Jern

    (University of Gothenburg
    Sahlgrenska University Hospital)

  • Mikael Landén

    (Karolinska Institutet
    The Sahlgrenska Academy at the University of Gothenburg)

  • Claudia Langenberg

    (University of Cambridge School of Clinical Medicine
    Berlin Institute of Health (BIH) at Charité—Universitätsmedizin Berlin
    Queen Mary University of London)

  • Ian J. Deary

    (University of Edinburgh)

  • Riccardo E. Marioni

    (The University of Edinburgh)

  • Stefan Enroth

    (Uppsala University)

  • Alexander P. Reiner

    (University of Washington)

  • George Dedoussis

    (Harokopio University of Athens)

  • Eleftheria Zeggini

    (Helmholtz Zentrum München—German Research Center for Environmental Health
    TUM School of Medicine and Health)

  • Sodbo Sharapov

    (Lomonosov Moscow State University
    Fondazione Human Technopole)

  • Yurii S. Aulchenko

    (Lomonosov Moscow State University
    Institute of Cytology and Genetics SB RAS)

  • Adam S. Butterworth

    (University of Cambridge
    University of Cambridge
    Wellcome Genome Campus and University of Cambridge
    University of Cambridge)

  • Anders Mälarstig

    (Karolinska Institutet
    Pfizer Worldwide Research, Development and Medical)

  • James F. Wilson

    (University of Edinburgh
    University of Edinburgh)

  • Pau Navarro

    (University of Edinburgh
    University of Edinburgh)

  • Xia Shen

    (Sun Yat-sen University
    Fudan University
    University of Edinburgh
    Fudan University)

Abstract

Understanding the genetic basis of neuro-related proteins is essential for dissecting the molecular basis of human behavioural traits and the disease aetiology of neuropsychiatric disorders. Here the SCALLOP Consortium conducted a genome-wide association meta-analysis of over 12,000 individuals for 184 neuro-related proteins in human plasma. The analysis identified 125 cis-regulatory protein quantitative trait loci (cis-pQTL) and 164 trans-pQTL. The mapped pQTL capture on average 50% of each protein’s heritability. At the cis-pQTL, multiple proteins shared a genetic basis with human behavioural traits such as alcohol and food intake, smoking and educational attainment, as well as neurological conditions and psychiatric disorders such as pain, neuroticism and schizophrenia. Integrating with established drug information, the causal inference analysis validated 52 out of 66 matched combinations of protein targets and diseases or side effects with available drugs while suggesting hundreds of repurposing and new therapeutic targets.

Suggested Citation

  • Linda Repetto & Jiantao Chen & Zhijian Yang & Ranran Zhai & Paul R. H. J. Timmers & Xiao Feng & Ting Li & Yue Yao & Denis Maslov & Anna Timoshchuk & Fengyu Tu & Emma L. Twait & Sebastian May-Wilson & , 2024. "The genetic landscape of neuro-related proteins in human plasma," Nature Human Behaviour, Nature, vol. 8(11), pages 2222-2234, November.
    • Handle: RePEc:nat:nathum:v:8:y:2024:i:11:d:10.1038_s41562-024-01963-z
    DOI: 10.1038/s41562-024-01963-z
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