ArticleACR open rheumatology2026
Rare Gain-of-Function Variants in IDH1 and IDH2 Confer Increased Risk of Immune-Mediated Rheumatic Diseases.
Article in ACR open rheumatology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Authors and funding
4 authors.
Funding
Abstract
objectiveGain-of-function variants in IDH1 and IDH2 are enriched among individuals with coexisting myeloid neoplasms and autoimmune diseases. However, the association between IDH1/IDH2 variants and rheumatic diseases independent of hematologic neoplasms remains unclear. We investigated the association between rare gain-of-function and loss-of-function genetic variants in IDH1 and IDH2 and immune-mediated rheumatic diseases.
methodsIndividuals with gain-of-function and loss-of-function variants in IDH1/IDH2 were identified by whole genome sequencing in the UK Biobank and the All of Us Research Program. These individuals were matched 1:10 to controls without IDH1 or IDH2 variants by age, sex, and ancestry. The frequency of immune-mediated rheumatic diseases in the presence and absence of IDH1/IDH2 variants was compared using chi-square or Fisher exact tests.
resultsFifty-five individuals with IDH1 or IDH2 gain-of-function variants without pre-existing hematologic neoplasms were identified in the UK Biobank. These individuals had a significantly higher frequency of incident immune-mediated rheumatic diseases compared to matched controls (11 of 55 [20%] vs 20 of 550 [4%], odds ratio [OR] = 6.6, P = 2.7 × 10
conclusionRare gain-of-function variants in IDH1/IDH2 are associated with increased risk of immune-mediated rheumatic diseases, particularly rheumatoid arthritis and polymyalgia rheumatica.
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