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

Marta Alcalde-Herraiz, Martí Català, Albert Prats-Uribe, Roger Paredes, JunQing Xie and Daniel Prieto-Alhambra ()
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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
JunQing Xie: University of Oxford
Daniel Prieto-Alhambra: University of Oxford

Nature Communications, 2024, vol. 15, issue 1, 1-10

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-52890-6

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