Genome-wide association study of BNT162b2 vaccine-related myocarditis identifies potential predisposing functional areas in Hong Kong adolescents

TL;DR

A genetic study in Hong Kong adolescents found potential genomic regions linked to BNT162b2 vaccine-related myocarditis, suggesting a genetic predisposition to this rare side effect.

Contribution

The study introduces a novel clustering approach and identifies specific functional genomic areas potentially linked to vaccine-related myocarditis in adolescents.

Findings

Genes related to cardiac conduction and ion channel activity were enriched in the analysis.

A novel clustering method identified 2,182 genomic regions overlapping with 1,499 genes.

The findings suggest a genetic predisposition to BNT162b2 vaccine-related myocarditis in specific functional areas.

Abstract

Vaccine-related myocarditis associated with the BNT162b2 vaccine is a rare complication, with a higher risk observed in male adolescents. However, the contribution of genetic factors to this condition remains uncertain. In this study, we conducted a comprehensive genetic association analysis in a cohort of 43 Hong Kong Chinese adolescents who were diagnosed with myocarditis shortly after receiving the BNT162b2 mRNA COVID-19 vaccine. A comparison of whole-genome sequencing data was performed between the confirmed myocarditis cases and a control group of 481 healthy individuals. To narrow down potential genomic regions of interest, we employed a novel clustering approach called ClusterAnalyzer, which prioritised 2,182 genomic regions overlapping with 1,499 genes for further investigation. Our pathway analysis revealed significant enrichment of these genes in functions related to cardiac conduction, ion channel activity, plasma membrane adhesion, and axonogenesis. These findings suggest a potential genetic predisposition in these specific functional areas that may contribute to the observed side effect of the vaccine. Nevertheless, further validation through larger-scale studies is imperative to confirm these findings. Given the increasing prominence of mRNA vaccines as a promising strategy for disease prevention and treatment, understanding the genetic factors associated with vaccine-related myocarditis assumes paramount importance. Our study provides valuable insights that significantly advance our understanding in this regard and serve as a valuable foundation for future research endeavours in this field.

The online version contains supplementary material available at 10.1186/s12863-024-01238-6.

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