Centre for Statistics in Medicine and NIHR Biomedical Research Centre Oxford, NDORMS, University of Oxford, Oxford, UK.
Department of Infectious Diseases and Institut de Recerca de la Sida IrsiCaixa, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain.
Nat Commun. 2024 Oct 9;15(1):8739. doi: 10.1038/s41467-024-52890-6.
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.
了解 COVID-19 疫苗血清转化率的遗传基础对于研究遗传因素对疫苗有效性的作用至关重要。在我们的研究中，我们使用英国生物银行的数据来寻找 COVID-19 疫苗诱导的血清阳性和突破性感染的遗传决定因素。我们对接种疫苗的参与者进行了四项全基因组关联研究，以研究 COVID-19 疫苗血清转化率和突破性感染易感性和严重程度。我们的研究结果证实了 HLA 区域与第一剂和第二剂后血清转化率之间的联系。此外，我们还确定了 10 个与突破性感染相关的基因组区域（SLC6A20、ST6GAL1、MUC16、FUT6、MXI1、MUC4、HMGN2P18-KRTCAP2、NFKBIZ 和 APOC1），以及一个与突破性严重程度相关的区域（APOE）。这些特征之间没有发现遗传局部化的显著证据。我们的研究强调了个体遗传构成在 COVID-19 疫苗产生不同抗体反应中的作用，并为疫苗接种后仍发生突破性感染的潜在机制提供了见解。
