Human leukocyte antigen (HLA) loci heterozygosity modulates genetic risk in idiopathic inflammatory myopathies
Authors' conclusion
This study identified significant nonadditive effects within the HLA region of IIM.
Study context
- Population
- IIM cases and controls of European ancestry
- Participants
- 3,206 vs 11,697
- Comparison
- IIM cases vs controls of European ancestry
- IIM casesn = 3,206
- Controlsn = 11,697reference
- Outcome
- Nonadditive effects (dominance and interaction) of HLA alleles on IIM risk
Methodological detailsHLA imputation using a multiancestry HLA reference panel, logistic regression, clinical subgroup analysis, stepwise conditional analyses
- HLA imputation using a multiancestry HLA reference panel
- Logistic regression
- Clinical subgroup analysis
- Stepwise conditional analyses
Main finding
As reported in the abstract
Significant nonadditive effects in 5 HLA genes, particularly core alleles of 8.1 AH
- HLA-B*08:01 nonadditive effect
- P = 3.93 × 10-13
- HLA-C*07:01 nonadditive effect
- P = 3.14 × 10-8
- HLA-DQA1*05:01 nonadditive effect
- P = 3.03 × 10-9
- HLA-DQB1*02:01 nonadditive effect
- P = 3.53 × 10-23
- HLA-DRB1*03:01 nonadditive effect
- P = 8.47 × 10-21
Observational data: associations, not effects.
Further findings
HLA-DRB1*03:01 risk in homozygotes vs heterozygotes
- Homozygote OR
- 2.17
- Heterozygote OR
- 3.13
Interaction model
- HLA-DQA1 and HLA-DRB1 showed specific significant allelic interactions
Phenotypic variance explained
- Nonadditive effect model explained a larger proportion of phenotypic variance than the additive-only model
Conditional analysis
- Independent nonadditive effect of HLA-DRB1*03:01 in 8.1 AH and amino acid residue Arg-74 in HLA-DRB1
Original publication
HLA loci heterozygosity modulates genetic risk in idiopathic inflammatory myopathies. Ann Rheum Dis. Published 30 July 2025. doi:10.
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