Omae Yosuke, Khor Seik-Soon, Shimada Mihoko, Kawai Yosuke, Yamaguchi Taihei, Yagi Maiko, Ebisawa Masashi, Takeuchi Junko S, Mizoue Tetsuya, Sugiura Wataru, Tokunaga Katsushi
Genome Medical Science Project, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, Singapore, Singapore.
Sci Rep. 2025 Apr 13;15(1):12728. doi: 10.1038/s41598-025-90787-6.
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). 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.
在接种新冠疫苗后的副作用方面已观察到个体差异，宿主遗传因素被认为是一个促成因素。在此，我们对2554名接受第三剂BNT162b2/辉瑞或mRNA - 1273/莫德纳疫苗的日本企业员工进行了全基因组关联研究（GWAS）。虽然在不良症状的存在方面未发现全基因组显著关联，但针对严重程度的GWAS揭示了6个相关位点。在淋巴结肿胀的严重程度与2号染色体q12位点之间观察到最显著的关联，该位点包括IL1RL1、IL18R1和IL18RAP基因（领先变异：rs76152249；P = 1.46×10）。通路分析表明，与包括HLA基因在内的MHC位点相关的免疫通路与发热的发生和严重程度之间存在关联，以及NF - κB结合通路与注射部位瘙痒的严重程度之间存在关联。此外，对先前关于新冠疫苗第一剂或第二剂的GWAS研究进行的荟萃分析揭示了来自72个位点的818个变异，这些变异与12种症状中的任何一种都表现出全基因组显著关联，并且通路分析确定了与MHC位点相关的免疫通路，这表明在初次接种和加强接种之间存在共同的遗传风险。这些结果可能有助于控制新冠疫苗接种后的副作用。
