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The immunoproteome and multimorbidity: A Mendelian randomization study.
Nikita Hukerikar1, Aroon D Hingorani2,3, Sandesh Chopade2,3
1Institute of Health Informatics, Faculty of Population Health Sciences, University College London, 222 Euston Road, London NW1 2DA, UK.
Science Advances
|May 20, 2026
Summary
This study reveals how immune proteins impact multiple diseases, identifying shared mechanisms and drug targets. Findings highlight opportunities for new treatments for conditions like heart disease and diabetes.
Area of Science:
- Immunology
- Genetics
- Pharmacology
Background:
- Multimorbidity, the presence of multiple chronic diseases, poses significant challenges in research and clinical practice.
- Understanding shared underlying mechanisms is crucial for developing effective treatments for complex health conditions.
Purpose of the Study:
- To investigate the influence of immune proteins on multiple diseases.
- To identify shared biological mechanisms and potential therapeutic targets for common diseases.
Main Methods:
- Utilized eight large plasma proteome Genome-Wide Association Studies (GWAS) to identify cis-acting variants for 151 immune proteins.
- Applied cis-Mendelian randomization to assess associations between immune proteins and 64 diseases/biomarkers.
- Constructed a knowledge graph to derive protein-disease communities, integrating association strength, druggability, and tissue-trait data.
Main Results:
- Identified immune proteins frequently associated with coronary heart disease, venous thromboembolism, atrial fibrillation, type 2 diabetes, and Parkinson's disease.
- Seven protein communities linked to pathways like ficolin binding and antimicrobial peptides, enriched for proteins affecting multiple diseases.
- Replicated associations with colocalization support for APOE, CD163, and IL-6R across neurodegenerative, cardiometabolic, and inflammatory traits.
Conclusions:
- Found strong genetic evidence for druggable immune proteins with pleiotropic effects across common diseases.
- Highlighted opportunities for expanding drug indications and developing novel therapeutics based on immune protein functions.
- Demonstrated the utility of integrating proteome-wide association studies and knowledge graphs for uncovering disease mechanisms.
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