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. 2025 Aug 25;11(3):e006035.
doi: 10.1136/rmdopen-2025-006035.

Shared genetic susceptibility between idiopathic inflammatory myopathies and common B cell lymphoma subtypes found primarily in the human leucocyte antigen region

Weng Ian Che  1 , Anton Öberg Sysojev  2 , Catherine Zhu  3 , Karina Patasova  2 ; International Lymphoma Epidemiology Consortium (InterLymph); IMACS Myositis Genetics Scientific Interest Group (MYOGEN); Karin E Smedby  2   4 , Ingrid E Lundberg  5   6 , Helga Westerlind  2 , Marie Holmqvist  7   6
Collaborators, Affiliations

Shared genetic susceptibility between idiopathic inflammatory myopathies and common B cell lymphoma subtypes found primarily in the human leucocyte antigen region

Weng Ian Che et al. RMD Open. .

Abstract

Objectives: To estimate shared genetic susceptibility between major subtypes of idiopathic inflammatory myopathies (IIM) and B cell lymphomas.

Methods: We paired summary statistics from genome-wide association studies (GWASs) of diffuse large B cell lymphoma, follicular lymphoma (FL), chronic lymphocytic leukaemia (CLL) and marginal zone lymphoma with those of dermatomyositis (DM) and polymyositis (PM) from a GWAS and an ImmunoChip study. We estimated local genetic correlation (rg) for each disease pair using local analysis of (co)variant association (Bonferroni-corrected p value<0.05) and identified genetic variants jointly associated with both diseases using pleiotropy-informed false discovery rate (conjunctional false discovery rate <0.05). Functional mapping and annotation analyses were also performed.

Results: We identified significant rg (ranging from -0.50 to 0.84) across 16 loci, with half located in the human leucocyte antigen (HLA) region, for the disease pairs of IIM and B cell lymphoma subtypes. Furthermore, jointly associated single-nucleotide polymorphisms were predominantly found in the HLA region. Specifically, all disease pairs showed shared genetic susceptibility in the HLA class I regions, while additional correlations in class III and class II regions were specific to DM and PM disease pairs, respectively. For some non-HLA loci with significant rg, functional analyses revealed immune-related responses potentially overlapping between DM and FL, DM and CLL, and PM and CLL.

Conclusion: We revealed that DM and PM share genetic susceptibility with common B cell lymphoma subtypes in both immune-related loci and loci with unclear biological functions. These novel findings improve our understanding of the pathological link between IIM and B cell lymphomas.

Keywords: Dermatomyositis; Epidemiology; Hematology; Polymorphism, Genetic; Polymyositis.

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Conflict of interest statement

Competing interests: IL and MH have received grants from Swedish Research Council. MH is a member of the medical advisory board of the Myositis Association. The other authors declare no conflicts of interest. The funding sources for the investigators from the IMACS Myositis Genetics Scientific Interest Group and the individual studies within the InterLymph consortium are listed in this manuscript and the online supplementary appendix, respectively.

Figures

Figure 1
Figure 1. Heatmaps presenting the local genetic correlations (rg) of all tested human leucocyte antigen loci for the GWAS (A) and the ImmunoChip (B) disease pairs of IIM and common B cell lymphoma subtypes. Common B cell lymphoma subtypes included diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL), chronic lymphocytic leukaemia (CLL) and marginal zone lymphoma (MZL); ***p value <0.00 (the threshold of significance); **p value <0.01; *p value <0.05. DM, dermatomyositis; GWAS, genome-wide association study; IIM, idiopathic inflammatory myopathy; PM, polymyositis.
See this image and copyright information in PMC

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