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Genetic analysis of over half a million people characterises C-reactive protein loci

Author

Listed:
  • Saredo Said

    (Imperial College London)

  • Raha Pazoki

    (Imperial College London
    Brunel University London
    Brunel University London
    Brunel University London)

  • Ville Karhunen

    (Imperial College London
    University of Oulu
    University of Oulu)

  • Urmo Võsa

    (Institute of Genomics, University of Tartu)

  • Symen Ligthart

    (University Hospital Antwerp)

  • Barbara Bodinier

    (Imperial College London)

  • Fotios Koskeridis

    (University of Ioannina Medical School)

  • Paul Welsh

    (University of Glasgow)

  • Behrooz Z. Alizadeh

    (University of Groningen and University Medical Centre Groningen)

  • Daniel I. Chasman

    (Brigham & Women’s Hospital
    Brigham and Women’s Hospital, Harvard Medical School)

  • Naveed Sattar

    (University of Glasgow)

  • Marc Chadeau-Hyam

    (Imperial College London
    Imperial College London)

  • Evangelos Evangelou

    (Imperial College London
    University of Ioannina Medical School)

  • Marjo-Riitta Jarvelin

    (Imperial College London
    University of Oulu)

  • Paul Elliott

    (Imperial College London
    Imperial College London
    UK Dementia Research Institute at Imperial College London, Burlington Danes Building, Hammersmith Hospital
    National Institute for Health Research Imperial Biomedical Research Centre, Imperial College London)

  • Ioanna Tzoulaki

    (Imperial College London
    University of Ioannina Medical School
    Imperial College London
    UK Dementia Research Institute at Imperial College London, Burlington Danes Building, Hammersmith Hospital)

  • Abbas Dehghan

    (Imperial College London
    Imperial College London
    UK Dementia Research Institute at Imperial College London, Burlington Danes Building, Hammersmith Hospital)

Abstract

Chronic low-grade inflammation is linked to a multitude of chronic diseases. We report the largest genome-wide association study (GWAS) on C-reactive protein (CRP), a marker of systemic inflammation, in UK Biobank participants (N = 427,367, European descent) and the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium (total N = 575,531 European descent). We identify 266 independent loci, of which 211 are not previously reported. Gene-set analysis highlighted 42 gene sets associated with CRP levels (p ≤ 3.2 ×10−6) and tissue expression analysis indicated a strong association of CRP related genes with liver and whole blood gene expression. Phenome-wide association study identified 27 clinical outcomes associated with genetically determined CRP and subsequent Mendelian randomisation analyses supported a causal association with schizophrenia, chronic airway obstruction and prostate cancer. Our findings identified genetic loci and functional properties of chronic low-grade inflammation and provided evidence for causal associations with a range of diseases.

Suggested Citation

  • Saredo Said & Raha Pazoki & Ville Karhunen & Urmo Võsa & Symen Ligthart & Barbara Bodinier & Fotios Koskeridis & Paul Welsh & Behrooz Z. Alizadeh & Daniel I. Chasman & Naveed Sattar & Marc Chadeau-Hya, 2022. "Genetic analysis of over half a million people characterises C-reactive protein loci," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29650-5
    DOI: 10.1038/s41467-022-29650-5
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    1. Clare Bycroft & Colin Freeman & Desislava Petkova & Gavin Band & Lloyd T. Elliott & Kevin Sharp & Allan Motyer & Damjan Vukcevic & Olivier Delaneau & Jared O’Connell & Adrian Cortes & Samantha Welsh &, 2018. "The UK Biobank resource with deep phenotyping and genomic data," Nature, Nature, vol. 562(7726), pages 203-209, October.
    2. Tune H. Pers & Juha M. Karjalainen & Yingleong Chan & Harm-Jan Westra & Andrew R. Wood & Jian Yang & Julian C. Lui & Sailaja Vedantam & Stefan Gustafsson & Tonu Esko & Tim Frayling & Elizabeth K. Spel, 2015. "Biological interpretation of genome-wide association studies using predicted gene functions," Nature Communications, Nature, vol. 6(1), pages 1-9, May.
    3. Kyoko Watanabe & Erdogan Taskesen & Arjen Bochoven & Danielle Posthuma, 2017. "Functional mapping and annotation of genetic associations with FUMA," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
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    Cited by:

    1. Fotios Koskeridis & Evangelos Evangelou & Saredo Said & Joseph J. Boyle & Paul Elliott & Abbas Dehghan & Ioanna Tzoulaki, 2022. "Pleiotropic genetic architecture and novel loci for C-reactive protein levels," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    2. Quan Sun & Bryce T. Rowland & Jiawen Chen & Anna V. Mikhaylova & Christy Avery & Ulrike Peters & Jessica Lundin & Tara Matise & Steve Buyske & Ran Tao & Rasika A. Mathias & Alexander P. Reiner & Paul , 2024. "Improving polygenic risk prediction in admixed populations by explicitly modeling ancestral-differential effects via GAUDI," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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