Abstract
Immune-mediated inflammatory diseases (IMID) are chronic conditions with a well-established multifaceted association with the gastrointestinal diseases Crohn’s disease (CD) and ulcerative colitis (UC), commonly known as inflammatory bowel disease (IBD). In this study, we leverage Danish nationwide pedigree and health data, genome-wide association studies, and fecal microbiota data to characterize the association between IBD and other IMIDs and disentangle genetic and environmental contributions. We show that CD and UC have distinct patterns of correlations with other IMIDs within families. By evaluating genetic and gut microbial correlations, we highlight a UC microbiota-linked correlation with multiple sclerosis and systemic lupus erythematosus despite a negative genetic correlation, suggesting a key role for environmental factors. In contrast, we find consistent genetic and microbial convergence between both IBD subtypes and rheumatoid arthritis, whereas genetic factors mainly drive the correlation with psoriasis. Thus, our findings uncover heterogeneity in shared etiological pathways across immune diseases, underscoring the need for stratified approaches to diagnosing and treating IBD.
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Data availability
This work uses data from the Danish National Health registries (https://sundhedsdatastyrelsen.dk), which is protected by the Danish Act on Processing of Personal Data to protect the personal sensitive data and adhere to the GDPR rules. An application to the Danish Health Data Agency is required to access data, which necessitates approval from your data responsible institution, which must be Danish. The application should only request data necessary to answer the research question, which must be for the benefit of society. You can expect a reply 5–8 weeks after submitting your application. Data should be delivered within 10 weeks. All other data sources are publicly available at GWAS Catalog, GWAS Atlas and NCBI’s BioProject database, and data access information is included in Supplementary Tables 4–6 or available from the authors. The raw numbers for charts and graphs are available in the Source Data files.
Code availability
All analyses were conducted in R (v4.4.0) and Python (v3.9.7). All generated code is available at GitHub: https://github.com/marievibeke/IBD_IMIDs_Correlation34.
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Acknowledgments
Danish National Research Foundation, DNRF148, TJ, and the Novo Nordisk Foundation, NNF21OC0068631, TJ. Figure 1 was generated by graphic designer Sabrina Hjort Andersen.
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M.V.V. conceptualized the study and was mainly responsible for all data handling and analyses. M.V.V. and A.A.N. wrote the first draft of the manuscript. G.A. supervised and assisted with the data handling and analysis of genealogy data. A.S. supervised the genetics analysis. T.J. was responsible for acquiring ethical permission to work with Danish healthcare data and provided access to data storage and computing resources. T.J. was further responsible for obtaining funding and supervised the entire work on the study. All authors were responsible for reviewing and editing the manuscript.
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TJ reports consultancy for Ferring and Pfizer. The remaining authors have no disclosures.
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Nature Communications thanks Simone Saibeni (eRef), who co-reviewed with Alice De Bernardi (ECR); Dalin Li and the other anonymous reviewer(s) for their contribution to the peer review of this work. A peer review file is available.
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Vestergaard, M.V., Alfaro-Núñez, A., Sazonovs, A. et al. Multimodal analysis disentangles the genetic and microbial associations between inflammatory bowel disease and other immune-mediated diseases across a harmonized population framework. Nat Commun (2026). https://doi.org/10.1038/s41467-026-68564-4
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DOI: https://doi.org/10.1038/s41467-026-68564-4
