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Genome-wide association studies of COVID-19 vaccine seroconversion and breakthrough outcomes in UK Biobank
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Genome-wide association studies of COVID-19 vaccine seroconversion and breakthrough outcomes in UK Biobank
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Journal Article
Genome-wide association studies of COVID-19 vaccine seroconversion and breakthrough outcomes in UK Biobank
2024
Overview
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.
Here, the authors use a large cohort to corroborate a link between genetic variants in the
HLA
region and COVID−19 vaccine responses, and locate 10 independent genetic loci significantly associated with breakthrough infection phenotypes after the vaccination. These findings support the notion that genetics play important roles in COVID−19 response and effectiveness.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 45/23
/ 45/43
/ Aged
/ Antibodies, Viral - immunology
/ Biobanks
/ COVID-19
/ COVID-19 - prevention & control
/ COVID-19 Vaccines - administration & dosage
/ COVID-19 Vaccines - immunology
/ Female
/ Genetics
/ Genome-wide association studies
/ Genome-Wide Association Study
/ Genomes
/ Histocompatibility antigen HLA
/ Humanities and Social Sciences
/ Humans
/ Male
/ Polymorphism, Single Nucleotide
/ Science
/ United Kingdom - epidemiology
/ Vaccines
