Genome-Wide Aggregated <i>Trans</i> Effects Analysis for Circulating Proteins Indicates a Key Role of Immune Checkpoints in Type 1 Diabetes
Demonstrating genetic evidence for a role of a protein in disease gives important support for its potential as a drug target. We aimed to identify proteins that have genetic evidence to support a causal role in the pathogenesis of type 1 diabetes. We found 27 core proteins had genetic evidence of causality for type 1 diabetes. Top hits included immune checkpoints (PDCD1, CD5, TIGIT, and LAG3) and innate immune system proteins (NCR1 and KLRB1). These results identify possible drug targets and suggest that programmed cell death protein 1 agonists should be trialed for type 1 diabetes prevention.
Authors
- Andrii Iakovliev (ORCID: https://orcid.org/0000-0003-4031-0073)
- Helen M. Colhoun (ORCID: https://orcid.org/0000-0002-8345-3288)
- Athina Spiliopoulou (ORCID: https://orcid.org/0000-0002-5929-6585)
- Paul McKeigue (ORCID: https://orcid.org/0000-0002-5217-1034)
- Caroline Hayward (ORCID: https://orcid.org/0000-0002-9405-9550)
- Buddhiprabha Erabadda (ORCID: https://orcid.org/0000-0003-4401-7149)
- Xuan Zhou (ORCID: https://orcid.org/0000-0003-3919-0342)
- Stuart J. McGurnaghan (ORCID: https://orcid.org/0000-0002-3292-4633)
Institutions
- Edinburgh Cancer Research (GB)
- Edinburgh College (GB)
- University of Edinburgh (GB)
Publication Details
- Journal
- Diabetes
- Published
- 2025-08-11
- DOI
- https://doi.org/10.2337/db25-0067
- Citations
- 1
- Primary Topic
- Diabetes and associated disorders
- Type
- article
- Field-Weighted Citation Impact
- 1.82
Funders
- Wellcome Trust
- Scottish Government
- British Heart Foundation
- Scottish Funding Council
- Diabetes UK
- Academy of Medical Sciences
- Chief Scientist Office, Scottish Government Health and Social Care Directorate
- Medical Research Council