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

Nat Commun. 2024 Oct 9;15(1):8739. doi: 10.1038/s41467-024-52890-6.

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.

MeSH terms

  • Aged
  • Antibodies, Viral* / blood
  • Antibodies, Viral* / immunology
  • Biological Specimen Banks*
  • COVID-19 Vaccines* / administration & dosage
  • COVID-19 Vaccines* / immunology
  • COVID-19* / epidemiology
  • COVID-19* / immunology
  • COVID-19* / prevention & control
  • Female
  • Genome-Wide Association Study*
  • HLA Antigens / genetics
  • HLA Antigens / immunology
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • SARS-CoV-2* / genetics
  • SARS-CoV-2* / immunology
  • Seroconversion*
  • UK Biobank
  • United Kingdom / epidemiology
  • Vaccination
  • Vaccine Efficacy

Substances

  • COVID-19 Vaccines
  • Antibodies, Viral
  • HLA Antigens