Genome-wide association study of common side effects following COVID-19 booster vaccination in a cohort of corporate employees in Japan

Abstract

Individual differences have been observed in side effects after vaccination for COVID-19, and host genetic factors have been suggested as a contributing factor. Here, we conducted a genome-wide association study (GWAS) involving 2,554 Japanese corporate employees who received a third booster dose of BNT162b2/Pfizer or mRNA-1273/Moderna vaccine. Although no genome-wide significant association was found for the presence of adverse symptoms, the GWAS for severity revealed six associated loci. The most significant association was observed between the severity of swelling of lymph nodes and chromosome 2q12 locus, including the IL1RL1, IL18R1, and IL18RAP genes (lead variant: rs76152249; P = 1.46 × 10^-9). Pathway analysis suggested associations between immune pathways related to the MHC locus, including HLA genes, and the occurrence and severity of fever, and the NF-κB binding pathway and those of itching at the injection site. In addition, a meta-analysis of previous GWAS studies for the primary first or second dose of COVID-19 vaccine revealed 818 variants from 72 loci that demonstrated genome-wide significant associations with any of 12 symptoms, and pathway analysis identified immune pathways related to the MHC locus, suggesting shared genetic risks among primary and booster vaccinations. These results may help control side effects following COVID-19 vaccination.

Keywords: COVID-19; Common side effects; GWAS; HLA; MHC locus; Vaccination.

Fig. 1

Manhattan plot for the association with the severity of local side effects or fever after booster vaccination with genome-wide significant associations. (A) Severity of swelling of lymph nodes (N = 2,459). (B) Severity of itching at injection site (N = 2,503). (C) Severity of induration at injection site (N = 2,213). (D) Severity of redness at injection site (N = 2,201). The red line indicates the genome-wide significance threshold (P = 5.0 × 10⁻⁸) and the blue line indicates the suggestive association threshold (P = 1.0 × 10⁻⁵).