Genome-Wide Risk Assessment and Clinical Prediction of Iodinated Contrast Media-Induced Anaphylaxis

Iodinated contrast media (ICM) are widely used in diagnostic imaging, but may trigger immediate hypersensitivity reactions, including anaphylaxis. Although human leukocyte antigen (HLA) associations have been proposed, genome-wide evidence remains limited. To identify genetic risk variants associated with ICM-induced anaphylaxis and evaluate their clinical utility.

We conducted a genome-wide association study (GWAS) in 91 Korean patients with confirmed ICM-induced anaphylaxis (discovery, n = 67; replication, n = 24) and 1,565 controls. Genotyping used a Korean-specific single nucleotide polymorphism (SNP) array. Significant variants were replicated. HLA alleles were imputed in the combined dataset. Linkage disequilibrium (LD) among significant loci was analyzed. Cumulative genetic burden was assessed by summing risk alleles per individual. A Least Absolute Shrinkage and Selection Operator-based prediction model incorporated genetic and clinical variables.

Nineteen SNPs reached genome-wide significance and were replicated, including rs2229629 in HK2 (odds ratio, 5.02; P = 9.6 × 10⁻²³), suggesting altered glycolysis. Additional variants were found near GABBR1, ZNF391, ATAT1, and HLA genes. Imputed HLA-DRB1*15:02 was significantly enriched in patients (41.8% vs. 5.9%, P = 5.21 × 10⁻¹⁷). LD analysis showed haplotypic clustering within HLA and non-HLA loci. A gene dosage effect was observed. The combined genetic-clinical model showed the highest predictive performance (area under the curve [AUC] = 0.888), exceeding genetic (AUC = 0.800) and clinical (AUC = 0.835) models.

This first GWAS of ICM-induced anaphylaxis identifies susceptibility loci across metabolic, immune, and neuroimmune pathways. HK2 was most strongly associated, and HLA-DRB1*15:02 was robustly replicated.