A web-based genome-wide association study reveals the susceptibility loci of common adverse events following COVID-19 vaccination in the Japanese population

The coronavirus disease 2019 (COVID-19) pandemic has spread rapidly worldwide. To prevent its spread, mRNA-based vaccines made by Pfizer/BioNTech (BNT162b1) and Moderna (mRNA-1273) have been widely used, including in Japan. Various adverse events have been reported following the COVID-19 mRNA vaccination, with differences observed among individuals. However, analyses of the genetic background associated with the susceptibility to side effects have been limited. In the present study, we performed genome-wide association studies (GWAS) for self-reported adverse events of the COVID-19 mRNA vaccination in 4545 Japanese individuals and identified 14 associated loci. Among these, 6p21 was associated with 37.5 °C or higher fever, 38 °C or higher fever, and muscle pain. HLA allele association analysis revealed that various HLA alleles were associated with the adverse effects; HLA-DQA1*03:01 and HLA-A*11:01 were more reliably associated with the adverse effects. Our results may enable the preparation and management of adverse effects by identifying the susceptibility to these adverse events. Furthermore, we obtained valuable data that may lead to a better understanding of the mechanisms of action of the COVID-19 mRNA vaccines.