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Genome-wide association studies of COVID-19 vaccine seroconversion and breakthrough outcomes in UK Biobank

Author

Listed:
  • Marta Alcalde-Herraiz

    (University of Oxford)

  • Martí Català

    (University of Oxford)

  • Albert Prats-Uribe

    (University of Oxford)

  • Roger Paredes

    (Hospital Universitari Germans Trias i Pujol
    Case Western Reserve University School of Medicine)

  • JunQing Xie

    (University of Oxford)

  • Daniel Prieto-Alhambra

    (University of Oxford
    Erasmus University Medical Centre)

Abstract

Understanding the genetic basis of COVID-19 vaccine seroconversion is crucial to study the role of genetics on vaccine effectiveness. In our study, we used UK Biobank data to find the genetic determinants of COVID-19 vaccine-induced seropositivity and breakthrough infections. We conducted four genome-wide association studies among vaccinated participants for COVID-19 vaccine seroconversion and breakthrough susceptibility and severity. Our findings confirmed a link between the HLA region and seroconversion after the first and second doses. Additionally, we identified 10 genomic regions associated with breakthrough infection (SLC6A20, ST6GAL1, MUC16, FUT6, MXI1, MUC4, HMGN2P18-KRTCAP2, NFKBIZ and APOC1), and one with breakthrough severity (APOE). No significant evidence of genetic colocalisation was found between those traits. Our study highlights the roles of individual genetic make-up in the varied antibody responses to COVID-19 vaccines and provides insights into the potential mechanisms behind breakthrough infections occurred even after the vaccination.

Suggested Citation

  • Marta Alcalde-Herraiz & Martí Català & Albert Prats-Uribe & Roger Paredes & JunQing Xie & Daniel Prieto-Alhambra, 2024. "Genome-wide association studies of COVID-19 vaccine seroconversion and breakthrough outcomes in UK Biobank," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52890-6
    DOI: 10.1038/s41467-024-52890-6
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    References listed on IDEAS

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    1. Claudia Giambartolomei & Damjan Vukcevic & Eric E Schadt & Lude Franke & Aroon D Hingorani & Chris Wallace & Vincent Plagnol, 2014. "Bayesian Test for Colocalisation between Pairs of Genetic Association Studies Using Summary Statistics," PLOS Genetics, Public Library of Science, vol. 10(5), pages 1-15, May.
    2. Junqing Xie & Beatriz Mothe & Marta Alcalde Herraiz & Chunxiao Li & Yu Xu & Annika M. Jödicke & Yaqing Gao & Yunhe Wang & Shuo Feng & Jia Wei & Zhuoyao Chen & Shenda Hong & Yeda Wu & Binbin Su & Xiaoy, 2024. "Relationship between HLA genetic variations, COVID-19 vaccine antibody response, and risk of breakthrough outcomes," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    3. 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.
    4. 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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