Fig. 3: An oligoprotein type I interferon signature derived from Olink proteomics and identification of interferonopathic autoimmune diseases in UK Biobank.
A Derivation of the MIRO score using Olink Explore 3072 analytes in UK Biobank. Circle packing of included interferon-stimulated genes (SIGLEC1, RIG-I, IFIT3) with area proportional to their absolute coefficient. Partly created in BioRender. Rioux, B. (2025) https://BioRender.com/zg7bcjo/. B Association of MIRO with controls and 21 common autoimmune diseases. Cross-sectional design of prevalent conditions (up to 10 years before baseline) in UK Biobank. Positive controls: interferon therapy, chronic viral hepatitis, organ/tissue transplant, HIV infection, liver and kidney disease. Negative control: haemorrhoids. Ten autoimmune conditions had a high (red) or moderate (blue) type I interferon signature (as per point estimates). Associations tested using linear regressions of MIRO (dependent variable) with each condition adjusted for potential confounders (two-sided tests). Data are presented as adjusted β (95% CI). Statistical significance defined as padj < 0.05 (adjusted for the number of tests within controls and autoimmunity separately). C Gene set enrichment analysis of MIRO across biological processes from MSigDB (hallmark) and classical ISGs. Rankings defined using Pearson’s correlation coefficients of MIRO with 2906 Olink analytes and classical ISGs defined using Chaussabel module 3.1. Normalised enrichment scores and FDR-adjusted p values (Benjamini–Hochberg procedure) obtained by gene set enrichment analysis. Source data are provided as a Source Data file. CI confidence interval, HIV human immunodeficiency virus, ISG interferon-stimulated gene, LASSO Least Absolute Shrinkage and Selection Operator, MIRO Markers of type I Interferon Response in Olink, MSigDB Human Molecular Signatures Database, padj false discovery rate adjusted p value (Benjamini–Hochberg procedure), SD standard deviation.
